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There is increasing interest in the African spiny mouse (Acomys cahirinus) as a model organism because of its ability for regeneration of tissue after injury in skin, muscle, and internal organs such as the kidneys. A high-quality reference genome is needed to better understand these regenerative properties at the molecular level. Here, we present an improved reference genome for A. cahirinus generated from long Nanopore sequencing reads. We confirm the quality of our annotations using RNA sequencing data from 4 different tissues. Our genome is of higher contiguity and quality than previously reported genomes from this species and will facilitate ongoing efforts to better understand the regenerative properties of this organism. [ABSTRACT FROM AUTHOR]

Abstract Background The Egyptian spiny mouse (Acomys cahirinus) is the only known rodent to exhibit true, human-like menstruation and postpartum ovulation, and is an important new model for reproductive studies. Spiny mice do not produce a visible copulatory plug, and calculation of gestational age is therefore restricted by the need to use mated postpartum dams. The current inefficient method of monitoring until parturition to provide a subsequent estimate of gestational age increases study duration and costs. This study addressed this issue by comparing the mating behaviour of spiny mice across the menstrual cycle and proposes a more accurate method for staging and pairing animals that provides reliable estimates of gestational age. In experiment 1, mating behaviour was recorded overnight to collect data on mounting, intromission, and ejaculation (n = 5 pairs per stage) in spiny mice paired at menses and at early and late follicular and luteal phases of the menstrual cycle. In experiment 2, female spiny mice were paired at the follicular or luteal phases of the menstrual cycle to determine any effect on the pairing-birth interval (n = 10 pairs). Results We report a broad mating window of ~ 3 days during the follicular phase and early luteal phase of spiny mice. Males displayed a discrete ‘foot twitch’ behaviour during intromission and a brief copulatory lock during ejaculation. Litters were delivered after 40–43 days if pairing occurred during the mating window, compared with 46–48 days for spiny mice paired in the late luteal phase. When pairing occurred during the late luteal phase or menses no mating activity was observed during the recording period. Conclusion This study clearly demonstrates an effect of the menstrual cycle on mating behaviour and pregnancy in the spiny mouse and provides a reliable and more effective protocol for estimating gestational age without the need for postpartum dams.

Despite the prevalence of large-group living across the animal kingdom, no studies have examined the neural mechanisms that make group living possible. Spiny mice, Acomys, have evolved to live in large groups and exhibit a preference to affiliate with large over small groups. Here, we determine the neural circuitry that facilitates the drive to affiliate with large groups. We first identify an anterior cingulate cortex (ACC) to lateral septum (LS) circuit that is more responsive to large than small groups of novel same-sex peers. Using chemogenetics, we then demonstrate that this circuit is necessary for both male and female group investigation preferences but only males' preference to affiliate with larger peer groups. Furthermore, inhibition of the ACC-LS circuit specifically impairs social, but not nonsocial, affiliative grouping preferences. These findings reveal a key circuit for the regulation of mammalian peer group affiliation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Current research using animal models to investigate retinal cell biology and model retinal degenerative diseases largely utilize small mammals that are nocturnal and lack the ability to restore lost vision. In contrast, the Mongolian gerbil (Meriones) is a diurnal rodent with good photopic vision, and the spiny mouse (Acomys) is a small desert-dwelling rodent with remarkable regenerative capabilities. The goal of this study was to identify antibodies that detect retinal cell classes in Meriones and Acomys , and to describe the retinal anatomy of these two species in comparison to outbred laboratory mice (Mus musculus). Immunohistochemistry was performed on retinal sections with antibodies for various retinal cell types. Sections were imaged by light, fluorescence, and confocal microscopy. Cell density, morphology, and placement were compared between species qualitatively and quantitatively. Our analyses revealed a classic assembly of retinal cells in Meriones and Acomys , with a few deviations compared to Mus. Meriones displayed the highest density of cones and Acomys the lowest. A higher density of bipolar cell bodies in the proximal portion of the inner nuclear layer was observed in both Acomys and Meriones compared to Mus , and both species exhibited an increase in amacrine cell density compared to Mus. Our results provide a foundation for future research into the visual system adaptations of these interesting species. • Comparisons of cell density between Acomys , Meriones and Mus musculus revealed that Meriones have the highest, and Acomys the lowest, density of cone photoreceptors, among the three species. • Both Meriones and Acomys display an increased density of bipolar cell bodies in the proximal portion of the INL relative to Mus , with Meriones having an overall increase in bipolar cell density. • Amacrine cells are present at higher density in both Meriones and Acomys relative the Mus. • We have identified a panel of commercially available antibodies that permit detection and quantification of retinal cell types in Acomys dimidiatus (the spiny mouse) and Meriones unguiculatus (the Mongolian gerbil). [ABSTRACT FROM AUTHOR]

Background: The Egyptian spiny mouse (Acomys cahirinus) is the only known rodent to exhibit true, human-like menstruation and postpartum ovulation, and is an important new model for reproductive studies. Spiny mice do not produce a visible copulatory plug, and calculation of gestational age is therefore restricted by the need to use mated postpartum dams. The current inefficient method of monitoring until parturition to provide a subsequent estimate of gestational age increases study duration and costs. This study addressed this issue by comparing the mating behaviour of spiny mice across the menstrual cycle and proposes a more accurate method for staging and pairing animals that provides reliable estimates of gestational age. In experiment 1, mating behaviour was recorded overnight to collect data on mounting, intromission, and ejaculation (n = 5 pairs per stage) in spiny mice paired at menses and at early and late follicular and luteal phases of the menstrual cycle. In experiment 2, female spiny mice were paired at the follicular or luteal phases of the menstrual cycle to determine any effect on the pairing-birth interval (n = 10 pairs). Results: We report a broad mating window of ~ 3 days during the follicular phase and early luteal phase of spiny mice. Males displayed a discrete 'foot twitch' behaviour during intromission and a brief copulatory lock during ejaculation. Litters were delivered after 40–43 days if pairing occurred during the mating window, compared with 46–48 days for spiny mice paired in the late luteal phase. When pairing occurred during the late luteal phase or menses no mating activity was observed during the recording period. Conclusion: This study clearly demonstrates an effect of the menstrual cycle on mating behaviour and pregnancy in the spiny mouse and provides a reliable and more effective protocol for estimating gestational age without the need for postpartum dams. [ABSTRACT FROM AUTHOR]

The vast majority of neural stem cell studies have been conducted on the brains of mice and rats, the classical model rodent. Non‐model organisms may, however, give us some important insights into how to increase neural stem cell numbers for regenerative purposes and with this in mind we have characterized these cells in the brain of the spiny mouse, Acomys cahirinus. This unique mammal is highly regenerative and damaged tissue does not scar or fibrose. We find that there are more than three times as many stem cells in the SVZ and more than 3 times as many proliferating cells compared to the CD‐1 outbred strain of lab mouse. These additional cells create thick stem cell regions in the wall of the SVZ and very obvious columns of cells moving into the rostral migratory stream. In the dentate gyrus, there are more than 10 times as many cells proliferating in the sub‐granular layer and twice the number of doublecortin expressing neuroblasts. A preliminary analysis of some stem cell niche genes has identified Sox2, Notch1, Shh, and Noggin as up‐regulated in the SVZ of Acomys and Bmp2 as being down‐regulated. The highly increased neural stem cell numbers in Acomys may endow this animal with increased regenerative properties in the brain or improved physiological performance important for its survival. [ABSTRACT FROM AUTHOR]

The details of how macrophages control different healing trajectories (regeneration vs. scar formation) remain poorly defined. Spiny mice (Acomys spp.) can regenerate external ear pinnae tissue, whereas lab mice (Mus musculus) form scar tissue in response to an identical injury. Here, we used this dual species system to dissect macrophage phenotypes between healing modes. We identified secreted factors from activated Acomys macrophages that induce a pro-regenerative phenotype in fibroblasts from both species. Transcriptional profiling of Acomys macrophages and subsequent in vitro tests identified VEGFC, PDGFA, and Lactotransferrin (LTF) as potential pro-regenerative modulators. Examining macrophages in vivo , we found that Acomys -resident macrophages secreted VEGFC and LTF, whereas Mus macrophages do not. Lastly, we demonstrate the requirement for VEGFC during regeneration and find that interrupting lymphangiogenesis delays blastema and new tissue formation. Together, our results demonstrate that cell-autonomous mechanisms govern how macrophages react to the same stimuli to differentially produce factors that facilitate regeneration. [Display omitted] • Acomys macrophages exhibit a reduced inflammatory phenotype • Secretory factors from Acomys macrophages induce regenerative fibroblast behavior • Macrophage-secreted VEGFC facilitates complex tissue regeneration in Acomys Macrophage secretory factors play distinct roles during tissue repair. Comparing tissue healing in spiny mice (regenerative) and laboratory mice (non-regenerative), Simkin and Aloysius et al. show that specific substances released by resident macrophages (e.g., VEGFC and LTF) facilitate complex tissue regeneration in spiny mice. [ABSTRACT FROM AUTHOR]

While spiny mice are primarily used as a model for Type II diabetes and for studying complex tissue regeneration, they are also an emerging model for a variety of studies examining hormones, behavior, and the brain. We began studying the spiny mouse to take advantage of their highly gregarious phenotype to examine how the brain facilitates large group-living. However, this unique rodent can be readily bred and maintained in the lab and can be used to ask a wide variety of scientific questions. In this brief communication we provide an overview of studies that have used spiny mice for exploring physiology and behavior. Additionally, we describe how the spiny mouse can serve as a useful model for researchers interested in studying precocial development, menstruation, cooperation, and various grouping behaviors. With increasingly available technological advancements for non-traditional organisms, spiny mice are well-positioned to become a valuable organism in the behavioral neuroscience community. • Spiny mice are a large group-living rodent amenable for lab studies. • Spiny mice have a unique physiology and are precocial and exhibit menstruation. • Spiny mice are highly prosocial in both reproductive and nonreproductive contexts. • Spiny mice are excellent for studying grouping and cooperative behavior. [ABSTRACT FROM AUTHOR]

Phylogeographic patterns in the Horn of Africa have recently attracted researchers searching for hidden diversity and explaining the evolutionary history of this region. In this paper, we focus on spiny mouse Acomys louisae. We examined 88 samples from 13 localities across Somaliland and sequenced CYTB, control region and IRBP genes. Phylogenetic analysis confirmed clear distinctness of A. louisae from the other clades of Acomys, but it also revealed deep splits within A. louisae clade. Samples from Central and Eastern Somaliland, including those from the type locality, form a clearly distinct Somaliland clade while remaining ones from the very NW of Somaliland and 5 previously published sequences from Djibouti and E Ethiopia form a Djibouti group. At two localities in the contact zone, we detected sympatric occurrence of both. The clades exhibit sharply contrasting patterns of variability, the Somaliland clade is characterized by a sufficient mitochondrial haplotype diversity, but low sequence divergence. The population parameters and haplotype networks suggest that the populations belonging to the Somaliland clade probably underwent a recent expansion of its range and population size. It may be explained by a repopulation after the interglacial period providing poor environmental conditions for spiny mice in E and C Somaliland. In contrast, the Djibouti group shows extremely high nucleotide diversity besides that of haplotype one. This suggests a long-term persistence of large and/or structured populations. It may be attributed to a specific history of the Ethiopian Rift and Afar. The results emphasize the importance of the Horn of Africa as a region preserving high endemism. [ABSTRACT FROM AUTHOR]

The spiny mouse, Acomys spp., is a recently described model organism for regeneration studies. For a mammal, it displays surprising powers of regeneration because it does not fibrose (i.e. scar) in response to tissue injury as most other mammals, including humans, do. In this Primer article, we review these regenerative abilities, highlighting the phylogenetic position of the spiny mouse relative to other rodents.We also briefly describe the Acomys tissues that have been used for regeneration studies and the common features of their regeneration compared with the typical mammalian response. Finally, we discuss the contribution that Acomys has made in understanding the general principles of regeneration and elaborate hypotheses as to why this mammal is successful at regenerating. [ABSTRACT FROM AUTHOR]

Wound‐induced hair follicle neogenesis (WIHN) has been demonstrated in laboratory mice (Mus musculus) after large (>1.5 × 1.5 cm2) full‐thickness wounds. WIHN occurs more robustly in African spiny mice (Acomys cahirinus), which undergo autotomy to escape predation. Yet, the non‐WIHN regenerative ability of the spiny mouse skin has not been explored. To understand the regenerative ability of the spiny mouse, we characterized skin features such as hair types, hair cycling, and the response to small and large wounds. We found that spiny mouse skin contains a large portion of adipose tissue. The spiny mouse hair bulge is larger and shows high expression of stem cell markers, K15 and CD34. All hair types cycle synchronously. To our surprise, the hair cycle is longer and less frequent than in laboratory mice. Newborn hair follicles in anagen are more mature than C57Bl/6 and demonstrate molecular features similar to C57Bl/6 adult hairs. The second hair cycling wave begins at week 4 and lasts for 5 weeks, then telogen lasts for 30 weeks. The third wave has a 6‐week anagen, and even longer telogen. After plucking, spiny mouse hairs regenerate in about 5 days, similar to that of C57Bl/6. After large full‐thickness excisional wounding, there is more de novo hair formation than C57Bl/6. Also, all hair types are present and pigmented, in contrast to the unpigmented zigzag hairs in C57Bl/6 WIHN. These findings shed new light on the regenerative biology of WIHN and may help us understand the control of skin repair vs regeneration. [ABSTRACT FROM AUTHOR]

Members of the Acomys genus, known as spiny mice, are unique among mammals in being perfectly capable of regenerating large areas of skin that have been removed. During this regenerative process hairs, sebaceous glands, erector pili muscles, adipocytes and the panniculus carnosus all regenerate and the dermis does not scar. We review here the processes that the epidermis and the individual components of the dermis undergo during spiny mouse regeneration as well as the molecules that have been identified as potentially important in regeneration. We then relate this to what has been proposed as playing a role in studies from the laboratory mouse, Mus musculus. Differences in the immune systems of spiny mice and laboratory mice are also highlighted as this is suggested to play a part not only in the perfect wound healing that embryos display but also in regeneration in lower vertebrates. [ABSTRACT FROM AUTHOR]

Study Question: Does the newly discovered menstruating spiny mouse exhibit behavioural and metabolic changes in correlation with premenstrual phases of the menstrual cycle?Summary Answer: This is the first report of cycle variability in the exploratory and interactive behaviour, and food consumption in menstruating spiny mice, and demonstrates that physiological changes are also dependent on within-subject variation.What Is Known Already: Premenstrual syndrome (PMS) is a prominent cyclic disorder that affects millions of women worldwide. More than 70% of women endure symptoms of impending menstruation, such as bloating, abdominal cramping and nausea to some degree. Consequently, ~8% of women experience recurrent physical and emotional symptoms which are extreme enough to disrupt daily life and seek intervention. Due to a lack of an appropriate animal model, the mechanisms underlying PMS are poorly understood, and subsequently, effective treatments are limited.Study Design, Size, Duration: This study analyses the changes in behavioural responses to the investigator during vaginal lavage (n = 14), exploratory behaviour (n = 11) and metabolism (n = 20) across the menstrual cycle in the spiny mouse (Acomys cahirinus).Participants/materials, Setting, Methods: We performed vaginal lavages on virgin spiny mice (6-8 months of age) and subjected each cohort of females to repeated measures for vaginal lavage, exploratory behaviour and metabolism. Stages of the menstrual cycle were designated as early follicular, late follicular, early luteal, late luteal, early menstrual and late menstrual, with the late luteal and early menstrual phases considered as premenstrual phases and analysed using generalized estimating equations. For vaginal lavage, the behavioural responses to researcher handling were scored on an increasing scale of severity during the lavage process (e.g. restraint, frequency of vocalizations, total handling time). For exploratory behaviour, exploration, memory and sociability were assessed through subjection to Open Field (OF), Novel Object Recognition (NORT), Social Novelty (SN) and Elevated Plus Maze (EPM) tests. For metabolism, physiological changes were measured over a 24-h period in metabolic cages. Results are mean ± SD with statistical significance set to P < 0.05.Main Results and the Role Of Chance: Qualitative behavioural assessment showed that compared to early follicular controls, during premenstrual phases, cycling females had significantly increased probability of: manifesting difficulties during restraint (4×, P < 0.01), vocalizing (8×, P < 0.01) and exhibiting isolation in the cage (40×, P = 0.041). We saw significant increases in handling time during the premenstrual phase in cycling females (76 ± 16 s) compared to controls (55 ± 7 s, P < 0.001). For exploratory behaviour, cycling females in their early menstrual phase travelled significantly less distance in the outer zone of the OF arena (13.3 ± 9.0 m) than females in their early luteal phase (22.3 ± 9.9 m, P = 0.038) and at significantly reduced velocities (40.2 ± 10.5 mm/s and 78.8 ± 31.0 mm/s, respectively, P = 0.006). These females also had fewer entries into the EPM open arms during the same phases (9.6 ± 6.1 and versus 20.0 ± 7.2, respectively, P = 0.030) and travelled less distance (3.2 ± 2.8 m versus 7.0 ± 5.5 m, respectively, P = 0.026). No differences were observed in NORT or SN across the cycle. In the metabolism studies, spiny mice demonstrated a significant increase in food consumption (percentage of body weight) during the early follicular and late luteal phases (3.9 ± 2.4% and 3.8 ± 2.1%, respectively) compared to the late follicular phase (2.3 ± 2.6%, P = 0.015).Large Scale Data: N/A.Limitations, Reasons For Caution: This is an observational study to determine fundamental changes in behaviour and metabolism in a novel species, and as such, lacks commercially available laboratory reagents and protocols specific to the spiny mouse.Wider Implications Of the Findings: The timing of these behavioural and physiological changes suggests that spiny mice exhibit symptoms analogous to PMS in higher order primates, thus providing a pre-clinical model for testing novel interventions to alleviate premenstrual symptoms and overcoming many limitations associated with this research area.Study Funding/competing Interest(s): N.B. is supported by a Research Training Program stipend through Monash University. J.E. is supported by a Fellowship awarded by the Peter Fielding Foundation. The Hudson Institute of Medical Research is supported by the Victorian Government Operational Research Infrastructure Support. The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

The spiny mouse, Acomys cahirinus, shows remarkable regenerative abilities after excisional skin wounding by regrowing hair, sebaceous glands, smooth muscle, skeletal muscle and dermis without scarring. We have asked here whether this same regeneration can be seen after full thickness thermal burn injuries. Using a brass rod thermal injury model we show that in contrast to the lab mouse, Mus musculus, which forms a thick scar covered by a hairless epidermis, the spiny mouse regenerates all the tissues injured - skeletal muscle, dermis, hairs, sebaceous glands such that the skin is externally indistinguishable from its original appearance. Re-epithelialization is faster in Acomys than in Mus but ingression and proliferation of dermal fibroblasts is the same in both species. After 3 weeks the wound epithelium of Acomys has developed a covering of new hair follicles in contrast to Mus. The skeletal muscle of the panniculus carnosus in Mus shows some regeneration but it is incomplete and fibrotic whereas the Acomys muscle is replaced perfectly. There are differences in the macrophage profiles which invade the damaged tissues such as the absence of F4/80 or MOMA-2 +ve cells in Acomys which likely reflect different cytokine profiles resulting from the same injury in these two species. [ABSTRACT FROM AUTHOR]

Study Question: Is the newly discovered menstruating rodent, the spiny mouse, a valid model for studying endometrial morphology and menstruation?Summary Answer: Our study is the first to demonstrate a primate-like pattern of natural menstruation in a rodent, with decidualization, spiral arteriole remodeling and piece-meal endometrial shedding.What Is Known Already: The spiny mouse has a naturally occurring menstrual cycle. This unique feature has the potential to reduce the heavy reliance on primates and provide a more appropriate small animal model for menstrual physiology research.Study Design, Size, Duration: This study compares morphological changes in the endometrium during early, mid and late menstruation of the spiny mouse (n = 39), human (n = 9) and the induced mouse model of menstruation (n = 17).Participants/materials, Setting, Methods: We assessed tissue morphology with hematoxylin and eosin and erythrocyte patterns with Mallory's trichrome. We conducted staining for neutrophil gelatinase associated lipocalin (NGAL), cytokeratin and interleukin-11 (IL-11) in all species. We used double immunofluorescence staining for vascular endothelial growth factor and alpha-smooth muscle actin to detect vasculature remodeling and western immunoblot to detect interleukin-8 (IL-8) and macrophage migration inhibitory factor (MIF) in the menstrual fluid of spiny mice.Main Results and the Role Of Chance: Menstruation occurs in the spiny mouse over a 72-h period, with heaviest menstrual breakdown occurring 24 h after initial observation of red blood cells in the vaginal cytology. During menstruation, the endometrium of the spiny mouse appeared to resemble human menstrual shedding with focal epithelial breakdown observed in conjunction with lysis of underlying stroma and detection of IL-8 and MIF in menstrual fluid. The mouse exhibits extensive decidualization prior to induced menses, with transformation of the entire uterine horn and cytokeratin expression absent until initiation of repair. Decidualization occurred spontaneously and was less marked in the spiny mouse, where epithelial integrity remained intact. In all species, the decidua was positive for IL-11 secretion and neutrophil recruitment was similar in each. Spiral arteriole formation was confirmed in the spiny mouse.Large Scale Data: N/A.Limitations, Reasons For Caution: This is a descriptive study comparing primarily morphological traits between the spiny mouse, the mouse and the human. Reagents specific to the spiny mouse were limited and resources for global use of this novel species are few.Wider Implications Of the Findings: Our work supports the spiny mouse as a viable model, sharing many attributes of physiological menstruation with humans. The strength of a natural as opposed to an artificial model is validated through the striking similarities observed between the spiny mouse and human in uterine breakdown. The spiny mouse may be highly useful in large-scale investigations of menstruation and menstrual disorders.Study Funding/competing Interest(s): N.B. and S.R. are each recipients of a Research Training Program scholarship supported by Monash University. This work was supported by the Victorian Government Operational Infrastructure and laboratory funds to H.D. The authors declare no competing interests. [ABSTRACT FROM AUTHOR]

This brief review considers the question of why some animals can regenerate and others cannot and elaborates the opposing views that have been expressed in the past on this topic, namely that regeneration is adaptive and has been gained or that it is a fundamental property of all organisms and has been lost. There is little empirical evidence to support either view, but some of the best comes from recent phylogenetic analyses of regenerative ability in Planarians which reveals that this property has been lost and gained several times in this group. In addition, a nonregenerating species has been induced to regenerate by altering only one signaling pathway. Extrapolating this to mammals it may be the case that there is more regenerative ability in mammals than has typically been thought to exist and that inducing regeneration in humans may not be as impossible as it may seem. The regenerative abilities of mammals is described and it turns out that there are several examples of classical epimorphic regeneration involving a blastema as exemplified by the regenerating Urodele limb that can be seen in mammals. Even the heart can regenerate in mammals which has long been considered to be a property unique to Urodeles and fish and several recent examples of regeneration have come from recent studies of the spiny mouse, Acomys, which are discussed here. It is suggested that a much more thorough phylogenetic analysis of mammalian regeneration would likely reveal some important insights into the evolution of regeneration. [ABSTRACT FROM AUTHOR]

Interferences into maternal nutrient are used in studies related to prenatal programming - the permanent changes in homeostasis of regulatory physiological mechanisms. In present study, the effect of HMB (β-hydroxy-β-methylbutyrate) maternal administration on body composition in newborn offspring of spiny mouse (Acomys cahirinus) was studied. The spiny mice were randomized into control (fed with a standard diet) and two experimental sub-groups additionally supplemented with HMB - 0.2 mg/kg of body weight per day in accordance with the time of HMB administration during gestation: period I lasting from the 13th to the 26th day of the gestation and period II lasting from day 26 to day 39 of gestation (lasting generally 39-40 days). Newborn spiny mice from the control group, the HMB I and HMB II groups were weighted and euthanized, and their organ weights were recorded. Maternal HMB-treatment did not significantly influence the body weight of newborns, although the offspring delivered by dams administered with HMB during middle gestation were significantly smaller compared to newborns delivered by dams treated with HMB during the last period of gestation. Lung and spleen weights were increased in the offspring delivered by HMB-treated dams irrespective of the period of administration. The weights of liver, kidneys and heart in the offspring delivered by HMB-treated dams in middle gestation were increased compared to the control group. This study showed a time-dependent maternal influence of HMB supplementation on the development of kidneys and liver. The increase in the weight of basal vital organs of newborn offspring in spiny mouse was not proportional to their body size. [ABSTRACT FROM AUTHOR]

Synthesis of dehydroepiandrosterone (DHEA) by the fetal adrenal gland is important for placental oestrogen production, and may also be important for modulating the effects of glucocorticoids on the developing brain. We have preciously shown that the enzymes and accessory proteins needed for DHEA synthesis—cytochrome P450 enzyme 17α-hydroxylase/17,20 lyase (P450c17), cytochrome-b5 (Cytb5), 3β-hydroxysteroid dehydrogenase (3βHSD)—are expressed in the adrenal gland from 30 days gestation, and DHEA, cortisol and aldosterone are present in fetal plasma from this time. Explant culture of fetal adrenal tissue showed that the spiny mouse adrenal gland, can synthesize and secrete DHEA from at least 0.75 of gestation, and suggest that DHEA may have an important role(s) in placental biosynthesis of oestrogens and in modulating the actions of glucocorticoids in the developing brain in this species. Post-natally, increased immuno-expression of P450c17 and Cytb5 expression in the zona reticularis of the adrenal gland and a significant increase in the synthesis and secretion of DHEA in plasma from 8 to 20 days of age in the spiny mouse, are representative of a period of high adrenal androgen production consistent with the human phenomenon of adrenarche. The studies summarised in this review also show that DHEA is produced de novo in the developing brain of the spiny mouse. These results showed that the spiny mouse brain can indeed produce DHEA from pregnenolone in a time-dependant manner, and coupled with the identification of P450c17 and Cytb5 protein in several regions of the brain, support the idea that DHEA is an endogenous neuro-active steroid in this species. Together, the studies outlined in this review indicate that the androgen DHEA is an important hormone of adrenal and Central Nervous System (CNS) origin in the fetal and postnatal spiny mouse. Disturbance of the development of these fetal tissues, and/or of the relationship between the fetal adrenal gland and placenta during pregnancy, may have significant consequences for fetal development, placental function, and maturation of the brain. It is proposed that such disturbances of normal adrenal function could account for some of the neuropathologies that arise in juvenile and adult offspring following illness and stress experienced by the mother during pregnancy. [ABSTRACT FROM AUTHOR]

Birth asphyxia or hypoxia arises from impaired placental gas exchange during labor and remains one of the leading causes of neonatal morbidity and mortality worldwide. It is a condition that can strike in pregnancies that have been uneventful until these final moments, and leads to fundamental loss of cellular energy reserves in the newborn. The cascade of metabolic changes that occurs in the brain at birth as a result of hypoxia can lead to significant damage that evolves over several hours and days, the severity of which can be ameliorated with therapeutic cerebral hypothermia. However, this treatment is only applied to a subset of newborns that meet strict inclusion criteria and is usually administered only in facilities with a high level of medical surveillance. Hence, a number of neuropharmacological interventions have been suggested as adjunct therapies to improve the efficacy of hypothermia, which alone improves survival of the post-hypoxic infant but does not altogether prevent adverse neurological outcomes. In this review we discuss the prospect of using creatine as a dietary supplement during pregnancy and nutritional intervention that can significantly decrease the risk of brain damage in the event of severe oxygen deprivation at birth. Because brain damage can also arise secondarily to compromise of other fetal organs (e.g., heart, diaphragm, kidney), and that compromise of mitochondrial function under hypoxic conditions may be a common mechanism leading to damage of these tissues, we present data suggesting that dietary creatine supplementation during pregnancy may be an effective prophylaxis that can protect the fetus from the multi-organ consequences of severe hypoxia at birth. [ABSTRACT FROM AUTHOR]

While regeneration occurs in a number of taxonomic groups across the Metazoa, there are very few reports of regeneration in mammals, which generally respond to wounding with fibrotic scarring rather than regeneration. A recent report described skin shedding, skin regeneration and extensive ear punch closure in two rodent species, Acomys kempi and Acomys percivali. We examined these striking results by testing the capacity for regeneration of a third species, Acomys cahirinus, and found a remarkable capacity to repair full thickness circular punches in the ear pinna. Four-millimeter-diameter wounds closed completely in 2 months in 100% of ear punches tested. Histology showed extensive formation of elastic cartilage, adipose tissue, dermis, epidermis and abundant hair follicles in the repaired region. Furthermore, we demonstrated abundant angiogenesis and unequivocal presence of both muscle and nerve fibers in the reconstituted region; in contrast, similar wounds in C57BL/6 mice simply healed the borders of the cut by fibrotic scarring. Our results confirm the regenerative capabilities of Acomys, and suggest this model merits further attention. [ABSTRACT FROM AUTHOR]

Neacomys (Sigmodontinae) comprises 8 species mainly found in the Amazonian region. We describe 5 new karyotypes from Brazilian Amazonia: 2 cytotypes for N. paracou (2n = 56/FNa = 62-66), 1 for N. dubosti (2n = 64/FNa = 68), and 2 for Neacomys sp. (2n = 58/FNa = 64-70), with differences in the 18S rDNA. Telomeric probes did not show ITS. We provide a phylogeny using Cytb, and the analysis suggests that 2n = 56 with a high FNa is ancestral for the genus, as found in N. paracou, being retained by the ancestral forms of the other species, with an increase in 2n occurring independently in N. spinosus and N. dubosti. Alternatively, an increase in 2n may have occurred in the ancestral taxon of the other species, followed by independent 2n-reduction events in Neacomys sp. and in the ancestral species of N. tenuipes, N. guianae, N. musseri, and N. minutus. Finally, a drastic reduction event in the diploid number occurred in the ancestral species of N. musseri and N. minutus which exhibit the lowest 2n of the genus. The karyotypic variations found in both intra- and interspecific samples, associated with the molecular phylogeny, suggest a chromosomal evolution with amplification/deletion of constitutive heterochromatin and rearrangements including fusions, fissions, and pericentric inversions. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Pregnancy induces adaptations in maternal metabolism to meet the increased need for nutrients by the placenta and fetus. Creatine is an important intracellular metabolite obtained from the diet and also synthesised endogenously. Experimental evidence suggests that the fetus relies on a maternal supply of creatine for much of gestation. However, the impact of pregnancy on maternal creatine homeostasis is unclear. We hypothesise that alteration of maternal creatine homeostasis occurs during pregnancy to ensure adequate levels of this essential substrate are available for maternal tissues, the placenta and fetus. This study aimed to describe maternal creatine homeostasis from mid to late gestation in the precocial spiny mouse. Methods: Plasma creatine concentration and urinary excretion were measured from mid to late gestation in pregnant (n = 8) and age-matched virgin female spiny mice (n = 6). At term, body composition and organ weights were assessed and tissue total creatine content determined. mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and the creatine transporter (CrT1) were assessed by RT-qPCR. Protein expression of AGAT and GAMT was also assessed by western blot analysis. Results: Plasma creatine and renal creatine excretion decreased significantly from mid to late gestation (P < 0.001, P < 0.05, respectively). Pregnancy resulted in increased lean tissue (P < 0.01), kidney (P < 0.01), liver (P < 0.01) and heart (P < 0.05) mass at term. CrT1 expression was increased in the heart (P < 0.05) and skeletal muscle (P < 0.05) at term compared to non-pregnant tissues, and creatine content of the heart (P < 0.05) and kidney (P < 0.001) were also increased at this time. CrT1 mRNA expression was down-regulated in the liver (<0.01) and brain (<0.01) of pregnant spiny mice at term. Renal AGAT mRNA (P < 0.01) and protein (P < 0.05) expression were both significantly up-regulated at term, with decreased expression of AGAT mRNA (<0.01) and GAMT protein (<0.05) observed in the term pregnant heart. Brain AGAT (<0.01) and GAMT (<0.001) mRNA expression were also decreased at term. Conclusion: Change of maternal creatine status (increased creatine synthesis and reduced creatine excretion) may be a necessary adjustment of maternal physiology to pregnancy to meet the metabolic demands of maternal tissues, the placenta and developing fetus. [ABSTRACT FROM AUTHOR]

Stable isotope analysis is frequently applied as a tool to examine dietary patterns in animals. However, some of the underlying assumptions associated with using this approach are increasingly being questioned. We carried out a controlled diet experiment on the southern African spiny mouse ( Acomys spinosissimus Peters, 1852) to test a number of aspects relating to these assumptions and also examine the hypothesis that stable isotopes, especially δ15N, can be used to provide evidence of nutritional stress. We compared the δ13C and δ15N values of livers and blood from animals that were fed ad libitum with animals undergoing a 10% reduction in food supply. Food-restricted animals showed no significant difference in δ15N; however, δ13C values of both liver and blood were depleted. Restricted animals also had a significantly lower C:N ratio. We examined the role of lipids and found following lipid extraction that both livers and lipids still showed the same separation in carbon values. Tissue-diet discrimination values were also calculated and found to be higher for both Δ13C and Δ15N compared with other mice species. Empirical values for discrimination rates were then compared with values calculated using an alternative method based on employing generic values and were found to be dissimilar, suggesting the use of generic values are not always appropriate. Our results highlight the need for greater understanding of the assumptions associated with using stable isotope analysis to examine diet and we suggest that studying a single species under captive conditions presents an ideal method to begin to test these hypotheses. [ABSTRACT FROM AUTHOR]

We studied the effects of early weaning on immunocompetence and parasite resistance in a precocial rodent Acomys cahirinus. We hypothesized that if parasite resistance is energetically expensive and nutritional and immunological support from mothers are necessary for the long-term health of offspring, then early weaned animals would be immunologically weaker and less able to defend themselves against parasites than later weaned animals. We weaned pups at 14, 21 or 28 days after birth and assessed their immunocompetence and resistance against fleas Parapulex chephrenis when they attained adulthood. Immunocompetence was assessed using leukocyte concentration (LC) and a phytohaemagglutinin injection assay (PHA test). To estimate resistance against fleas, we measured performance of fleas via the number of produced eggs and duration of development and resistance to starvation of the flea offspring. We found a significant positive effect of weaning age on the PHA response but not on LC. The effect of age at weaning on flea egg production was manifested in male but not female hosts, with egg production being higher if a host was weaned at 14 than at 28 days. Weaning age of the host did not affect either duration of development or resistance to starvation of fleas produced by mothers fed on these hosts. We conclude that even in relatively precocial mammals, weaning age is an important indicator of future immunological responses and the ability of an animal to resist parasite infestations. Hosts weaned at an earlier age make easier, less-resistant targets for parasite infestations than hosts weaned later in life. [ABSTRACT FROM AUTHOR]

An increased incidence of mental illness disorders is found in children and adolescents born to mothers who experienced an infection-based illness during pregnancy. Animal models to study the prenatal origin of such outcomes of pregnancy have largely used conventional rodents, which are immature (altricial) at birth compared with the human neonate. In this study, we used the precocial spiny mouse (Acomys cahirinus), whose offspring have completed organogenesis at birth, and administered a single subcutaneous injection of a 5 mg/kg dose of the viral mimetic poly I:C (polyriboinosinic-polyribocytidylic acid) at mid gestation (20 days; term is 39 days). Prenatal exposure to poly I:C caused a transient weight loss in the pregnant dam, produced a downregulation of the proinflammatory cytokine tumour necrosis factor-α in the fetal brain, and resulted in abnormalities in sensorimotor gating and reduced social interaction, memory and learning in juvenile offspring. No changes in exploratory activity or anxiety and fear behaviours were found between the treatment groups. This study provides evidence that, in a rodent model that more closely resembles human brain development, prenatal infection can lead to behavioural abnormalities in postnatal life. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The circadian rhythm of locomotory activity in the Arabian spiny mouse, a desert living species, was investigated under controlled laboratory conditions. Ten individuals were subjected to successive light cycles. When subjected to a 12L:12D light cycle, locomotor activity was confined mainly to the dark phase (mean 94.2% ± 1.6%). During a period of constant darkness (DD), all animals expressed free running rhythms of locomotor activity (mean 23h49 ± 0h04). Following a second LD cycle, the light and dark phases were inversed (12D:12L). Activity shifted with the lights and was masked during the light phase, re-entrainment was rather slow (up to 10 days). The effect of varying ambient temperature (20–35 °C) on the locomotor activity under a 12L:12D cycle revealed that temperature had no distinct effect on the level of locomotor activity. When the dark component of the day was lengthened to 8L:16D, the mean percentage of activity during the dark increased to 96.0 ± 0.8%, while a significant decrease in night time activity was observed when the dark phase length was decreased to 16L:8D (78.29 ± 2.52%). The Arabian spiny mouse therefore behaves as other desert dwelling rodents and can be described as truly nocturnal. [ABSTRACT FROM AUTHOR]

Regeneration of adult mammalian central nervous system (CNS) axons is abortive, resulting in inability to recover function after CNS lesion, including spinal cord injury (SCI). Here, we show that the spiny mouse (Acomys) is an exception to other mammals, being capable of spontaneous and fast restoration of function after severe SCI, re-establishing hind limb coordination. Remarkably, Acomys assembles a scarless pro-regenerative tissue at the injury site, providing a unique structural continuity of the initial spinal cord geometry. The Acomys SCI site shows robust axon regeneration of multiple tracts, synapse formation, and electrophysiological signal propagation. Transcriptomic analysis of the spinal cord following transcriptome reconstruction revealed that Acomys rewires glycosylation biosynthetic pathways, culminating in a specific pro-regenerative proteoglycan signature at SCI site. Our work uncovers that a glycosylation switch is critical for axon regeneration after SCI and identifies β3gnt7 , a crucial enzyme of keratan sulfate biosynthesis, as an enhancer of axon growth. [Display omitted] • Acomys spontaneously regains motor and urinary functions following complete SCI • The Acomys SCI site shows abundant axon regeneration and nerve conduction • Acomys assembles a pro-regenerative environment with rewired ECM glycosylation • β3gnt7 is a novel axon regeneration enhancer Nogueira-Rodrigues et al. report that Acomys can recover function after complete spinal cord injury (SCI), assembling a scarless tissue at the injury site, unlike other adult mammals. Transcriptomic analysis of the SCI site shows that injured Acomys builds a specific pro-regenerative proteoglycan signature with a unique glycosylation network. [ABSTRACT FROM AUTHOR]

Animals show daily rhythms in most bodily functions, resulting from the integration of information from an endogenous circadian clock and external stimuli. These rhythms are adaptive and are expected to be related to activity patterns, i.e., to be opposite in diurnal and nocturnal species. Melatonin is secreted during the night in all mammalian species, regardless of their activity patterns. Consequently, in diurnal species the nocturnal secretion of melatonin is concurrent with the resting phase, whereas in nocturnal species it is related to an increase in activity. In this research, we examined in three diurnal and three nocturnal rodent species whether a daily rhythm in anxiety-like behavior exists; whether it differs between nocturnal and diurnal species; and how melatonin affects anxiety-like behavior in species with different activity patterns. Anxiety-like behavior levels were analyzed using the elevated plus-maze. We found a daily rhythm in anxiety-like behavior and a significant response to daytime melatonin administration in all three nocturnal species, which showed significantly lower levels of anxiety during the dark phase, and after melatonin administration. The diurnal species showed either an inverse pattern to that of the nocturnal species in anxiety-like behavior rhythm and in response to daytime melatonin injection, or no rhythm and, accordingly, no response to melatonin. [ABSTRACT FROM AUTHOR]

The genus Acomys is represented by 19 species in a vast area in the African and eastern Mediterranean regions. Acomys cilicicus, belonging to the genus Acomys, is an endemic species in Turkey. In this study, by evaluating the reproductive data in laboratory conditions and the natural habitat of A. cilicicus, the reproductive biology of the species was researched in detail for the first time. The data concerning the reproduction of 1404 samples, reproduced from 1 male and 2 females in the laboratory and 34 samples obtained from 6 localities near Silifke, were recorded. For A. cilicicus, it was determined that the pregnancy period was 38-40 days, litter size was 1-3 (n = 321, mean = 2.05), and time to maturity was 2-4 months. The newborns' eyes were closed, their auricles were bonded to the head, they had short hair, their abdomens were hairless, and their backs were dark gray. Dentition was completed within 9-10 days and therefore the newborn could easily take food. Suckling was under control of the mother and carried on for approximately 2-3 months. Furthermore, the reproductive, infanticidal, and cannibalistic behaviors of this species were monitored periodically. These data were compared with A. cahirinus, russatus, nesiotes, minous, and dimidiatus, whose reproductive biologies are known and who are close to A. cilicicus geographically. Finally, it was determined that some reproductive findings of A. cilicicus were compatible with the findings of other species, and some findings were different from those of the species above. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: It has been hypothesized that male fetuses down regulate placental growth during periods of accelerated fetal growth. We aimed to investigate this, and determine whether sexual dimorphism was apparent in the spiny mouse placenta. We hypothesized that expression of fetal growth promoters would be higher in placentas of males, whereas genes involved in placental structural development would be more highly expressed in placentas of females. Methods: Spiny mouse dams, a precocial rodent with an in utero endocrine milieu dissimilar from other rodents, but akin to humans, were sacrificed at gestational ages 15–37 (term = 39 days). Placentas were collected and processed for histology or qPCR analysis of selected genes (GCM1, MAP2K1, SLC2A1, NR3C1, IGF1, IGF1R). Results: Fetal and placental weights were similar for both sexes. Placentas of female fetuses had less spongy zone (P SEX < 0.0001), and more labyrinth (P SEX < 0.0001) than males. Early placenta and labyrinth expression of SLC2A1 was higher in males than females (P SEX < 0.05). Labyrinthine IGF1R remained constant until term in the female, compared with male where expression increased until term. Peak MAP2K1 expression occurred earlier in the male placenta than the female. Spongy zone SLC2A1 remained constant until term in the female, compared with male where expression increased until term. Conclusions: The spiny mouse is a species that exhibits sexually dimorphic placental development. We suggest that these sex differences in placental gene expression and structure may underlie or compound the male vulnerability to a sub-optimal in utero environment. [Copyright &y& Elsevier]

Abstract: Epidemiological studies have suggested a link between prenatal exposure to bacterial or viral infections and subsequent development of mental disorders such as schizophrenia and autism. Animal models to study the prenatal origin of such outcomes of pregnancy have largely used conventional rodents which are immature at birth compared to the human neonate, and doses of the infective agent (i.e., lipopolysaccharide, Poly I:C) have been large enough to cause sickness behaviour in the mother. In this study we have used the spiny mouse (Acomys cahirinus) whose offspring have completed organogenesis at birth, and a single subcutaneous injection of a low (0.5mg/kg) dose of polyriboinosinic–polyribocytidilic acid (Poly I:C) at mid gestation (20days, term is 39days). The treatment had no effect on maternal, fetal or neonatal survival, or postnatal growth of the offspring. However, offspring showed significant impairments in non-spatial memory and learning tasks, and motor activity. Brain histology examined at 1 and 100days of age revealed significant decreases in reelin, increased GFAP expression, and increased numbers of activated microglia, specifically in the hippocampus. This study provides evidence that a prenatal subclinical infection can have profound effects on brain development that are long-lasting. [Copyright &y& Elsevier]

Abstract: Studies of human neonates, and in animal experiments, suggest that birth asphyxia results in functional compromise of the hippocampus, even when structural damage is not observable or resolves in early postnatal life. The aim of this study was to determine if changes in hippocampal function occur in a model of birth asphyxia in the precocial spiny mouse where it is reported there is no major lesion or infarct. Further, to assess if, as in human infants, this functional deficit has a sex-dependent component. At 37 days gestation (term=39 days) spiny mice fetuses were either delivered immediately by caesarean section (control group) or exposed to 7.5min of in utero asphyxia causing systemic acidosis and hypoxia. At 5 days of age hippocampal function was assessed ex vivo in brain slices, or brains were collected for examination of structure or protein expression. This model of birth asphyxia did not cause infarct or cystic lesion in the postnatal day 5 (P5) hippocampus, and the number of proliferating or pyknotic cells in the hippocampus was unchanged, although neuronal density in the CA1 and CA3 was increased. Protein expression of synaptophysin, brain-derived neurotrophic factor (BDNF), and the inositol trisphosphate receptor 1 (IP3R1) were all significantly increased after birth asphyxia, while long-term potentiation (LTP), paired pulse facilitation (PPF), and post-tetanic potentiation (PTP) were all reduced at P5 by birth asphyxia. In control P5 pups, PPF and synaptic fatigue were greater in female compared to male pups, and after birth asphyxia PPF and synaptic fatigue were reduced to a greater extent in female vs. male pups. In contrast, the asphyxia-induced increase in synaptophysin expression and neuronal density were greater in male pups. Thus, birth asphyxia in this precocial species causes functional deficits without major structural damage, and there is a sex-dependent effect on the hippocampus. This may be a clinically relevant model for assessing treatments delivered either before or after birth to protect this vulnerable region of the developing brain. [Copyright &y& Elsevier]

This study was designed to determine follicular atresia in the newborn and the prepubertal spiny mouse. We analyzed the processes of follicle loss using classical markers of apoptosis (TUNEL reaction, active caspase-3) and autophagy (Lamp1). Numerous small clear vacuoles and autophagosomes as well as strong Lamp1 staining were observed in dying oocytes of all follicle types, especially of the primordial and primary ones. Active caspase 3 and the TUNEL reaction were detected only in the granulosa cells of large secondary and antral follicles. The expression of apoptosis and autophagy markers was also changing during the prepubertal period. Western blot analysis indicated that at the moment of birth, females undergo an increased rate of follicular atresia mediated by autophagy, while apoptosis is the dominant form of ovarian atresia in consecutive postnatal days. On the basis of these observations, we concluded that apoptosis and autophagy are involved in follicular atresia and these processes are cell and developmental stage-specific. [ABSTRACT FROM AUTHOR]

Abstract: The possible role of increased dietary salinity as a proximate regulator of reproduction in xeric population of golden spiny mice (Acomys russatus) and mesic population of common spiny mice (A. cahirinus) was tested. In the wild, as the dry season progresses, evaporative water loss in the vegetation increases. This leads to increase in particle concentration of plant tissues. Thus, species consuming a plant diet are exposed to increased dietary salinity. Both male and female individuals of A. russatus were subjected to gradually increasing dietary salinity (0.9%, 2.5%, 3.5%, and 5%) while those of A. cahirinus only up to 3.5% for a total period of 8 and 6 weeks, respectively. Urine osmolarity showed a significant increase under 3.5% and 5% salinity in A. russatus and 2.5% and 3.5% in A. cahirinus. Testis mass and spermatogenesis were significantly reduced while uterine mass and vaginal estrus cycles were not affected in A. russatus. None of the parameters was significantly affected in A. cahirinus. Increase in salinity also significantly reduced body mass in A. russatus but not in A. cahirinus. Mass-specific daily digestible energy intake was not significantly affected by increased salinity in both species. Recovery individuals regained body mass quickly and surpassed initial values after four weeks. However, testis mass and spermatogenesis did not show recovery. The results suggest that increase in dietary salinity could be used as a proximate signal to regulate reproduction in A. russatus by halting it in males, as the dry season progresses while such role in the mesic population of A. cahirinus is unlikely. [Copyright &y& Elsevier]

Abstract: Circadian locomotor rhythms were examined in adult common spiny mice, Acomys cahirinus. Spiny mice demonstrated nocturnal activity, with onset of activity coinciding promptly with onset of darkness. Re-entrainment to 6-h delays of the light–dark cycle was accomplished faster than to 6-h advances. Access to running wheels yielded significant changes in period and duration of daily activity. Novelty-induced wheel running had no effect on phase of activity rhythms. Circadian responses to light at various times of the circadian cycle were temporally similar to those observed in other nocturnal rodent species. No gender differences were observed in any of the parameters measured. [Copyright &y& Elsevier]

The common spiny mice Acomys dimidiatus and golden spiny mice Acomys russatus coexist in the extreme warm and dry parts of the Rift Valley in Israel. However, they are temporally segregated in that the former is nocturnal, whereas the latter is diurnal. Daily rhythms of physiological and behavioral variables in A. russatus responded to semiochemical signals released by A. dimidiatus (in the urine and feces). Both species feed upon the same food items but at different times of the 24-hr cycle. The main aim of the present study was to test under field conditions the foraging response of A. russatus to odors of different ages released by A. dimidiatus. Various feeding and behavioral variables were compared in three groups of A. russatus. The results show that fresh semiochemical signals released by A. dimidiatus decrease the feeding efficiency and increase the rate of smelling from a distance in A. russatus. These results support the idea that temporal segregation between the two coexisting species is at least partly through semiochemicals present in the urine and feces. [ABSTRACT FROM AUTHOR]