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The multimammate mouse ( Mastomys natalensis; M. natalensis ) has been identified as a major reservoir for multiple human pathogens including Lassa virus (LASV), Leishmania spp., Yersinia spp., and Borrelia spp. Although M. natalensis are related to well-characterized mouse and rat species commonly used in laboratory models, there is an absence of established assays and reagents to study the host immune responses of M. natalensis . As a result, there are major limitations to our understanding of immunopathology and mechanisms of immunological pathogen control in this increasingly important rodent species. In the current study, a large panel of commercially available rodent reagents were screened to identify their cross-reactivity with M. natalensis. Using these reagents, ex vivo assays were established and optimized to evaluate lymphocyte proliferation and cytokine production by M. natalensis lymphocytes. In contrast to C57BL/6J mice, lymphocytes from M. natalensis were relatively non-responsive to common stimuli such as phytohaemagglutinin P and lipopolysaccharide. However, they readily responded to concanavalin A stimulation as indicated by proliferation and cytokine production. In summary, we describe lymphoproliferative and cytokine assays demonstrating that the cellular immune responses in M. natalensis to commonly used mitogens differ from a laboratory-bred mouse strain.

Improved husbandry and better knowledge of exotic pets have led to a gradual increase in the life span of pets, such as rats, mice, hamsters, and gerbils. Much of the information on these senior patients is derived from the laboratory animal studies and anecdotal practitioner information. Although the small size of some of the patients makes blood collection problematic for hematology and organ function testing, the advent of polymerase chain reaction testing and other molecular diagnostics is allowing practitioners to test for specific etiologies with the small biologic samples available. Radiology and ultrasonography also are valuable diagnostic modalities., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Causes of morbidity and mortality and a survey of infectious disease agents were collated from wild and colony-raised endangered Amargosa voles ( Microtus californicus scirpensis ). Six voles from the wild and 295 voles in the captive-breeding colony were included in the study upon identification of an infectious agent during screening, identification of clinical signs of disease, or finding a pathological condition or infectious agent on necropsy. Findings included 28 significant or incidental pathological conditions of seven organ systems and 19 parasitic, viral, bacterial, or fungal agents. Several voles captured in the wild had fungal osteomyelitis of the tail that disseminated systemically in a vole brought from the wild to the colony and may have been caused by a Penicillium sp. Three voles reintroduced from the colony to the wild experienced inanition and subsequent severe hepatic and moderate renal tubular lipidosis. The most common significant pathological conditions in colony-reared voles were chronic interstitial nephritis with proteinosis; cardiomyopathy; trichobezoars that, in intestines or cecocolic junctions, sometimes induced local rupture or infarction with peritonitis; multifocal gastrointestinal ulceration and colibacillosis; acute renal tubular necrosis or nephritis; sepsis; hepatic and renal lipidosis; molar apical elongation sometimes progressing to invasion of the calvarium; and mammary tumors. Uncommon diagnoses included intervertebral disc disease; microvascular dysplasia; and multifocal bacterial abscessation. Common or clinically important infectious agents included Demodex sp. mites in hair follicles, Demodex sp. in esophageal mucosa, and an outbreak of tropical rat mites thought to have been introduced via the straw bedding; gastrointestinal Helicobacter sp.; attaching and effacing Escherichia coli ; and Citrobacter braakii , a possible zoonotic bacterium. This survey of species-specific diseases and pathogens was possible because the established health surveillance program that is part of the species recovery plan allowed for monitoring of voles throughout the duration of their natural life spans in captivity.

Multiple adult female CB6F1 mice presented with supernumerary incisors after preconditioning with chemotherapy and total body irradiation for bone marrow transplantation (BMT). Mice received nonmyeloablative total body irradiation (3 Gy) and either cyclophosphamide or bendamustine, followed by BMT and posttransplantation cyclophosphamide or bendamustine. Here we describe the clinical presentation, μCT findings, and histopathologic evaluation of the affected mice. These analyses confirmed the gross diagnosis and revealed details of the abnormal tooth morphology. We surmise that the combination of total body irradiation and chemotherapy resulted in the abnormal formation of supernumerary incisors. Supernumerary teeth should be considered as a potential confounding factor in tracking weight loss after BMT. These conditions can be managed to allow animals to reach their intended scientific endpoint.

The authors present eight cases of gastric dilatation and volvulus (GDV) in guinea pigs from the Department and Clinic of Exotic Animal and Wildlife Medicine, University of Veterinary Medicine, Budapest, Hungary between 2012 and 2016. Seven animals were operated on and two survived. Gastric torsion has been noted in many mammalian species. Gastric volvulus has a high morbidity and high mortality rate with a guarded to poor prognosis in all of these species. How GDV develops is still not widely understood. Postmortem examinations, in both our cases and previously reported cases, have failed to reveal the exact causes of the gastric torsions. The aetiology of gastric torsion in guinea pigs is probably multifactorial. Feeding fewer meals per day, eating rapidly, decreased food particle size, exercise, stress after a meal, competition, age, and an aggressive or fearful temperament, are all likely and potential risk factors for GDV development in a similar fashion to dogs. Sex, breeding, dental diseases, anatomical abnormalities, pain and pregnancy may also be contributing factors.

The black rat (Rattus rattus) is an invasive species and potential reservoir of significant pathogens of man, domestic animals and wildlife. During the 2012-2014 austral summers, 201 black rats were captured and examined on the uninhabited Guafo Island, in Northern Chilean Patagonia (43.593029°S, 74.713481°W). The mite Ornithonyssus bacoti caused lymphoplasmacytic and eosinophilic dermatitis in all infected rats (105/210, 52%), but no skin lesions were observed in rats infected with Nosopsyllus spp. and Plocopsylla spp. fleas. Eighty-eight rats (44%) had mild lymphoplasmacytic and eosinophilic enterocolitis and 61 of these rats were infected with the nematode Heterakis spumosa. In the liver, 63 animals (31%) had areas of necrosis with histiocytic and eosinophilic inflammation associated with multiple Calodium hepaticum eggs, and in 15 cases there was co-infection with several Taenia taeniaeformis strobilocerci. Mild interstitial lymphoplasmacytic sialadenitis with intranuclear inclusion bodies, suggesting cytomegalovirus infection, was observed in 28 rats (15%). In the lung, alveolar histiocytosis (69 rats, 34%) and perivascular lymphocytic infiltrates (46 rats, 23%) were the most common findings. There was mild to moderate lymphoplasmacytic interstitial nephritis in 52 rats (26%) and in 15% of these cases Leptospira spp. antigen was detected in the distal renal tubules. Some of the diseases of black rats on Guafo Island are likely to play a role in rat population dynamics. The endemic Guafo Island long-clawed mole mouse (Geoxus lafkenche), sea lions and fur seals may be at risk for infection by some of these rat pathogens., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Marsh rice rats (Oryzomys palustris) fed a pelleted diet high in sucrose and casein have been used as a model for moderate to severe periodontitis. Here we characterize the prevalence, location, and histopathologic features of food-impaction lesions (FIL), a unique type of oral event, in rice rats fed standard pelleted rodent chow from weaning until 34 wk of age. Healthy female rats (n = 90; age, 4 wk) were weaned into groups (n = 10 to 24) and were euthanized at 4, 16, 22, 28, or 34 wk of age. At necropsy, high-resolution photographs of the 4 jaw quadrants were examined by 3 independent observers to determine the presence, number, and location of FIL. In addition, gross periodontitis was scored (scale, 0 to 4), and the hemimaxillar surface area containing FIL was measured. Serial sections of decalcified jaws were assessed histologically. The prevalence of FIL increased with age, and was 0% (baseline), 59.1%, 69.6%, 81.8% and 80.0% in rats at age 4, 16, 22, 28, and 34 wk, respectively. FIL were predominantly located (93.9%) in the maxillary palatal surfaces of the interproximal area between molars 2 and 3 and did not affect mandibular surfaces. The percentage of the hemimaxillar surface area occupied by FIL was 6.83%, 4.82%, 2.88%, and 6.52% in rats at age 16, 22, 28, and 34 wk, respectively. Histopathologic changes in FIL varied from localized gingivitis to larger, localized periodontitis-like lesions. These data indicate that FIL are common in rice rats fed standard rodent chow, are slight to mild in severity, and are localized to specific regions in the oral cavity, thus suggesting they may be a suitable model for local maxillary periodontitis when fed standard rodent chow.

Background: Many women experience menstrual migraines that develop into recurrent migraine attacks during menstruation. In the human menstrual cycle, the estrogen level fluctuates according to changes in the follicular and luteal phases. The rat estrous cycle is used as an animal model to study the effects of estrogen fluctuation., Objective: To investigate whether the estrous cycle is involved in migraine development by comparing the neuronal excitability of trigeminal ganglion (TG) neurons in each stage of the estrous cycle., Material and Method: Female rats were divided into four experimental groups based on examinations of the cytologies of vaginal smears, and serum analyses of estrogen levels following each stage of the estrous cycle. The rats in each stage of the estrous cycle were anesthetized and their trigeminal ganglia were removed The collections of trigeminal ganglia were cultured for two to three hours, after which whole-cell patch clamp experiments were recorded to estimate the electrophysiological properties of the TG neurons., Results: There were many vaginal epithelial cells and high estrogen levels in the proestrus and estrus stages of the estrous cycle. Electrophysiological studies revealed that the TG neurons in the proestrus and estrus stages exhibited significantly lower thresholds of stimulation, and significant increase in total spikes compared to the TG neurons that were collected in the diestrus stage., Conclusion: Our results revealed that high estrogen levels in the proestrus and estrus stages altered the thresholds, rheobases, and total spikes of the TG neurons. High estrogen levels in the estrous cycle induced an increase in neuronal excitability and the peripheral sensitization of TG neurons. These findings may provide an explanation for the correlation of estrogen fluctuations during the menstrual cycle with the pathogenesis of menstrual migraines.

Whereas early investigations into ulcerative dermatitis (UD) focused on the possibility of a primary dermatopathology, several recent studies have advocated scratching behavior as a primary driver for UD. The aim of this study was to assess whether B6 mice exhibit excessive scratching under resting conditions or when provoked by epidermal barrier disruption. We hypothesized that B6 mice would exhibit more spontaneous scratching behavior and that B6 mice would be more pruritic after mild epidermal barrier injury compared with the other strains and stock tested. The behavior of the retired breeder female C57BL/6J, DBA/2J, BALB/cByJ, and Crl:CD1 mice was videotaped for 60 min. Behavior filming occurred at 17:15 and at 07:00 the next morning prior to (baseline) and after tape-stripping to initiate epidermal barrier disruption. Scratching duration was recorded as brief (less than 3 s) or prolonged (3 s or longer), on the basis of observations during a pilot study. In contrast to the hypothesis, B6 mice did not scratch significantly more frequently, have more long-duration scratching events, nor have a higher median scratching duration of prolonged scratching as compared with the other types of mice tested. In fact, B6 mice showed the lowest average scratching frequency and duration under both conditions. B6 mice demonstrated increased scratching behavior after epidermal barrier disruption, but the increased scratching did not surpass the rate or duration of scratching in the other types of mice tested. These findings do not support the idea that a strain-related tendency toward exaggerated scratching behavior under resting or epidermal barrier disruption conditions predisposes B6 mice to UD.

Ulcerative dermatitis (UD) is a spontaneous idiopathic disease that often affects C57BL/6 mice or mice on a C57BL/6 background. UD is characterized by intense pruritus and lesion formation, most commonly on the head or dorsal thorax. Self-trauma likely contributes to wound severity and delayed wound healing. Histologically, changes are nonspecific, consisting of ulceration with neutrophilic and mastocytic infiltration and epithelial hyperplasia and hyperkeratosis. Diet appears to have a profound effect on the development and progression of UD lesions. We investigated the incidence and severity of UD in C57BL/6NCrl mice on a high-fat western-style diet (HFWD) compared with a standard rodent chow. In addition, we examined the protective effects of dietary supplementation with a multimineral-rich product derived from marine red algae on UD in these 2 diet groups. HFWD-fed mice had an increased incidence of UD. In addition, mice on a HFWD had significantly more severe clinical and histologic lesions. Dietary mineral supplementation in mice on a HFWD decreased the histologic severity of lesions and reduced the incidence of UD in female mice in both diets. In conclusion, a high-fat western-style diet may potentiate UD in C57BL/6NCrl mice. Insufficient mineral supply and mineral imbalance may contribute to disease development. Mineral supplementation may be beneficial in the treatment of UD.

Elodontoma was diagnosed in two pet guinea pigs, one involving a maxillary premolar tooth and the other affecting a mandibular incisor tooth. Diagnostic imaging, including radiographs, computed tomography, and oral endoscopy was performed in order to quantify dental disease. Diagnostic imaging was also used to guide treatment of acquired dental disease, which included intraoral restoration of normal occlusal plane and tooth extraction using an extraoral approach. These are the first histologically confirmed cases of elodontoma in guinea pigs.

Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE(1), and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring.

To study spontaneous intraocular hemorrhage in rats during postnatal ocular development and to elucidate the underlying mechanism, postnatal ocular development in the albino Wistar Hannover (WH) and Sprague-Dawley (SpD) and pigmented Long-Evans (LE) strains was analyzed. Pups (n = 2 to 5) from each strain were euthanized daily on postnatal days (PND) 0 through 21 and their eyes examined macroscopically and histologically; similar analyses were performed in 26 to 39 additional WH pups daily from PND 7 to 14. At necropsy, ring-shaped red regions and red spots were present in the eyes of WH and SpD rats. These lesions were attributed histologically to hemorrhage of the tunica vasculosa lentis or of the retina, choroid, and hyaloid artery, respectively. Similar intraocular hemorrhages occurred in LE rats, although the macroscopic alterations found in WH and SpD rats were not present in this strain. Among the 3 strains evaluated, the incidence of the intraocular hemorrhage was highest in WH rats. We here showed that intraocular hemorrhage occurs spontaneously during normal ocular development in rats regardless of the strain; however, the region, degree, and incidence of intraocular hemorrhage differ among strains. Hemorrhage in the tunica vasculosa lentis and hyaloid artery may result from the leakage of erythrocytes from the temporary vasculature of these tissues during regression. The mechanisms underlying hemorrhage in the retina and choroid remain unclear. To our knowledge, this report is the first to describe the spontaneous intraocular hemorrhage that occurs during postnatal ocular development in rats.

The aim of this study was to evaluate a newly developed infrared side-stream capnograph with minimal sample volume for the continuous measurement of end-tidal carbon dioxide (CO2) concentrations in small rodents. Thirty-four male Wistar rats (weight 345 ± 70 g) were treated in accordance with the National Institutes of Health (NIH) guidelines for animal care. All experiments were performed with approval of the local animal care and use committee. Sepsis was induced by implanting an 18 gauge stent into the colon 24 h prior to the experiments, allowing a constant fecal leakage into the peritoneal cavity (25 septic and nine control animals). Hemodynamic variables and end-tidal CO2 were recorded continuously and arterial blood (5 × 120 µL) was sampled periodically for arterial blood gas analysis. After baseline controlled mechanical ventilation was randomized and titrated to either normocapnia (35-45 mmHg) or hypercapnia (65-75 mmHg) with exogenous application of CO2. A total of 155 paired CO2 measurements comparing end-tidal and arterial partial pressure were conducted. Side-stream capnography underestimated the CO2 partial pressure with a bias of -6.1 mmHg and a 95% limit of agreement from 6.7 to -19.1 mmHg. Our results suggest that side-stream end-tidal CO2 monitoring with a low dead space could be utilized in rats as a surrogate for the arterial CO2 measurement over a wide range of partial pressures in normal and septic animals.

The objective of this study was to evaluate the changes in electroencephalographic (EEG) power spectrum in response to decapitation of anaesthetized rats, in order to assess the nociception or otherwise of this procedure. Ten young adult male Sprague-Dawley rats were anaesthetized with halothane in oxygen and anaesthesia was maintained at a stable concentration of halothane between 1.20% and 1.25%. The rat's head and neck were placed through the opening of a small animal guillotine so that the blade of the guillotine was positioned over the atlanto-occipial joint of the rat's neck. The EEG was recorded in a five-electrode montage, bilaterally. After recording a 15 min baseline the rat was decapitated by swiftly pressing the guillotine blade and the EEG recording was continued until the signal was isoelectric on both channels. Changes in the median frequency (F50), 95% spectral edge frequency (F95) and total power of the EEG (Ptot) were used to investigate the effects of decapitation. During the first 15 s following decapitation, there were significant increases in the F50 and F95, and a decrease in the Ptot compared with baseline values. There was a clear window of time immediately following decapitation where changes in the EEG frequency spectrum were obvious; these changes in the EEG indices of nociception could be attributed as responses generated by the rat's cerebral cortex following decapitation.

A total of 207 wild rodents were caught on nine pig farms, five chicken farms and five non-farm locations in Sweden and surveyed for a selection of bacteria, parasites and viruses. Lawsonia intracellularia and pathogenic Yersinia enterocolitica were only detected in rodents on pig farms (9% and 8% prevalence, respectively) which indicate that these agents are more likely to be transmitted to rodents from pigs or the environment on infected farms. Brachyspira hyodysenteriae (1%), Brachyspira intermedia (2%), Campylobacter jejuni (4%), Campylobacter upsaliensis (2%), leptospires (7%) and encephalomyocarditis virus (9%) were also detected from rodents not in contact with farm animals. Giardia and Cryptosporidium spp. were common, although no zoonotic types were verified, and Salmonella enterica was isolated from 1/11 mice on one farm but not detected by PCR from any of the rodents. Trichinella spp. and Toxoplasma gondii were not detected.

To examine the prevalence of human pathogens carried by rats in urban areas in Hanoi and Hai Phong, Vietnam, we live-trapped 100 rats in January 2011 and screened them for a panel of bacteria and viruses. Antibodies against Leptospira interrogans (22·0%), Seoul virus (14·0%) and rat hepatitis E virus (23·0%) were detected in rats, but antibodies against Yersinia pestis were not detected. Antibodies against L. interrogans and Seoul virus were found only in adult rats. In contrast, antibodies to rat hepatitis E virus were also found in juvenile and sub-adult rats, indicating that the transmission mode of rat hepatitis E virus is different from that of L. interrogans and Seoul virus. Moreover, phylogenetic analyses of the S and M segments of Seoul viruses found in Rattus norvegicus showed that Seoul viruses from Hai Phong and Hanoi formed different clades. Human exposure to these pathogens has become a significant public health concern.

This paper proposes an estimation procedure for the semiparametric accelerated failure time frailty model that combines smoothing with an Expectation and Maximization-like algorithm for estimating equations. The resulting algorithm permits simultaneous estimation of the regression parameter, the baseline cumulative hazard, and the parameter indexing a general frailty distribution. We develop novel moment-based estimators for the frailty parameter, including a generalized method of moments estimator. Standard error estimates for all parameters are easily obtained using a randomly weighted bootstrap procedure. For the commonly used gamma frailty distribution, the proposed algorithm is very easy to implement using widely available numerical methods. Simulation results demonstrate that the algorithm performs very well in this setting. We re-analyz several previously analyzed data sets for illustrative purposes., (Copyright © 2012 John Wiley & Sons, Ltd.)

Dental disease is prevalent in the captive degu (Octodon degus), yet little has been documented on the variety of disorders in this species. In this internet-based study, dental cases presented over a 7-year period were collated, analyzed, and grouped. Of the 137 total cases, the most common dental disorder of the degu was found to be molar malocclusion (42.3 %). Other disorders documented included enamel decoloration (13.1%), molar elodontoma (8.0%), enamel hypoplasia (6.6%), incisor tooth fracture (6.6%), incisor malocclusion (3.6%), oral abscess (2.2%), and impacted molar teeth (0.7%). Details of each condition, pathogenesis, and clinical signs are described. Age was found not to be a significant predictor of dental disease in the degu.

The main aim of this study was to investigate the impact of pelleted diet of different mineral composition on the sonographic and CT appearance of kidneys in degus (Octodon degus). A total of 35 animals were randomly divided into five groups, fed diets containing different calcium and phosphorus contents (13.5 g/kg calcium and 6.3 g/kg phosphorus, or 9.1 g/kg calcium and 9.5 g/kg phosphorus) and given different amounts of exposure to UV light. Endoscopic examination of the oral cavity as well as renal ultrasonography and CT was performed four times at four-month intervals throughout the study. After 14 months of feeding an experimental diet, all degus were euthanased and subsequently all kidneys were collected for histopathological examination. Animals fed a diet with high dietary phosphate and improper calcium to phosphorus ratio showed severe nephrocalcinosis. Ultrasonographic and CT kidney abnormalities presented as hyperechogenicity and hyperdensity (interpreted as nephrocalcinosis), respectively. The most striking changes were seen at the corticomedullary zone. Ultrasonography and CT correlated in all cases with histopathological findings. Dental disease developed quickly in groups fed diets with an improper calcium and phosphorus content, with obvious apical and coronal elongation of all the teeth. A possible influence of UV light access could not be proved in this study.

Ulcerative dermatitis (UD) is a common, spontaneous condition in mice with a C57BL/6 background. Although initial lesions may be mild, UD is a progressive disease that often results in ulcerations or debilitating fibrotic contractures. In addition, lesions typically are unresponsive to treatment. Euthanasia is often warranted in severe cases, thereby affecting study outcomes through the loss of research subjects. Because the clinical assessment of UD can be subjective, a quantitative scoring method and documentation of the likely time-frame of progression may be helpful in predicting when animals that develop dermatitis should be removed from a study. Such a system may also be helpful in quantitatively assessing success of various treatment strategies and be valuable to clinical laboratory animal veterinarians. In this 1.5-y, prospective cohort study, we followed 200 mice to monitor the development and course of UD. Mice were examined every 2 wk. A clinical sign (alopecia, pruritus, or peripheral lymphadenopathy) was not identified that predicted development of UD lesions in the subsequent 2-wk period. Once UD developed, pruritus, the character of the lesion (single or multiple crust, coalescing crust, erosion, or ulceration), and the size of the lesion were the only parameters that changed (increased) over the course of the disease. Pruritus was a factor in the rapid progression of UD lesions. We used these findings to develop a quantitative scoring system for the severity of UD. This enhanced understanding of the progression of UD and the quantitative scoring system will enhance the monitoring of UD.

Trypanosoma evansi infections in domestic animals are characterized by anemia and thrombocytopenia. The cause of the platelets decrease is unknown, but researchers suggest that thrombocytopenia may result from damage of the bone marrow, reduced survival of platelets, auto-immune thrombocytopenia, disseminated intravascular coagulation and splenic sequestration. Some of these causes have already been tested by our research group and found to be unrelated. Therefore, this study has the objective of testing the hypothesis that splenic sequestration might be responsible for thrombocytopenia in T. evansi-infected rats. A total of 28 rats assigned to four groups were used in the experiment. Group A rats were splenectomized and infected with T. evansi, group B rats were infected with T. evansi, group C rats were splenectomized, but not infected and group D rats were normal controls. Five days post-infection all rats were anesthetized and blood was collected in order to measure the number of circulating platelets, fibrinogen levels, prothrombin time (PT) and activated partial thromboplastin time (aPTT). The spleens of groups B and D were weighed at necropsy. The infected animals (groups A and B) showed a significant reduction in platelets and increased PT and aPTT when compared to negative control groups (groups C and D). Animals from group A showed increased levels of fibrinogen. The mean weight of spleen differed between group B (2.62g) and group D (0.55g). It was concluded that there is no relationship between thrombocytopenia and splenic sequestration in infection by T. evansi., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Damaraland mole rats (Cryptomys damarensis) are among the longest-living rodents, with a maximum longevity of approximately 16 years. As one of the few mammals termed eusocial, these animals have been used in behavioral, genetic, metabolic, and physiologic research at the University of Connecticut since 1997. For individual identification at 3 to 4 months of age, mole rats were subcutaneously implanted with microchip transponders (11 mm in length) in the dorsal cervical region. In 2007, 2 of the 90 implanted adults, 10-year-old and 9-year-old females, developed subcutaneous masses at the site of the implant. Histopathological and immunohistochemical examinations revealed amelanotic melanoma and fibrosarcoma, respectively, with metastasis of the amelanotic melanoma. In 2008, a total of 3 adult males were castrated as part of a sex behavior study; 3 months later, all 3 castrated males developed subcutaneous masses around their implants, whereas none of the noncastrated males had masses. After an additional 9 months, these masses were found to be granulomas. To the authors' knowledge, this is the first report of neoplasia in this species. Both the tumors and the granulomas surrounded the microchip transponder., (© The Authors 2011)

Gastric volvulus has been documented in several species of animals and is associated with high morbidity and mortality. We report 2 cases of gastric volvulus in guinea pigs that died without detection of prior clinical signs. Both guinea pigs were adult female guinea pigs in a breeding colony and had given birth to multiple litters; one was pregnant at the time of death. Gastric rotations of 540° and 360° were identified at necropsy examination. These cases include the first known report of gastric rotation greater than 360° in any species. Although gastric volvulus has been reported to occur in guinea pigs, little is known about its risk factors, etiology, and pathogenesis. We conducted a literature review to compare gastric volvulus between guinea pigs and other species., (Copyright 2011 by the American Association for Laboratory Animal Science)

The impact of pelleted diets with different mineral compositions on the crown size of the mandibular cheek teeth, as well as the mandibular bone and cheek teeth density, in degus (Octodon degus) was investigated. A total of 28 animals were randomly divided into four groups and fed different calcium or phosphorous dietary content, in the presence or absence of UV light, for 14 months. Dental radiographs and CT images of the head were taken, and the crown size of premolar and molar teeth was recorded. Apical and coronal crown elongation of all cheek teeth and significantly smaller relative cheek teeth and mandibular densities were recorded in degus fed a high-phosphorus diet with an improper calcium:phosphorus ratio. A diet with a calcium:phosphorus ratio of 1:1 was also responsible for the rapid development of dental disease with subsequent severe health impairment.

The purpose of this article is to provide for practitioners a comprehensive overview of respiratory diseases, both infectious and noninfectious, in the mouse, rat, hamster, and gerbil. The information presented will also be useful for veterinarians pursuing board certification. Anatomy and physiology are briefly addressed, as those two facets alone could encompass an entire article for these species., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Respiratory diseases are common in guinea pigs and chinchillas. There are multifactorial causes of respiratory involvement in these species of rodents, from infectious (bacterial, viral, and fungal) to neoplastic causes. Toxicoses and diseases affecting other systems may also induce respiratory signs. Knowledge of biology, including husbandry, nutritional requirements, and behavior, are important clues for the clinician to determine the role these issues may play in the development, progression, and prognosis of respiratory clinical cases in rodents. Current approaches in the diagnosis and therapy for respiratory disease in small mammals warrant more research concerning response-to-treatment reports., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Degus are commonly used as laboratory animals; however, over the past few years, they have become increasingly popular as pets., Objectives: The aim of this article was to present disease prevalence in 300 pet degus divided in two age groups (under and above two years)., Methods: Medical records of degus (Octodon degus), which were presented to the author's clinic in the period from January 2007 to December 2009, were reviewed., Results: The most common diseases in degus were (1) acquired dental disease (60·0%) with significantly higher prevalence in older animals (P<0.001), (2) skin alopecia due to fur chewing (13·33%) and (3) lens cataracts (13·33%). Other common disorders included traumatic injuries to soft tissues (bite wounds and tail slip), traumatic fractures and dietary diarrhoea. Reproductive disorders were most commonly associated with dystocia and pathological changes in the post-natal period. Only 38 degus in a total of 300 animals were healthy., Clinical Significance: This is the first study to describe the disease prevalence in two age groups of pet degus. The majority of diseases were caused by improper diet, self-mutilation and improper handling; as such client education is necessary to avoid such a high disease prevalence., (© 2011 British Small Animal Veterinary Association.)

Veterinarians are confronted with a variety of food and nutrition-related skin diseases, with cutaneous food adverse reaction the most common in small animal dermatology. In addition to canine atopic dermatitis, cutaneous food adverse reaction has been an area of interest for extensive research for the last decade. Nutritional deficiencies and toxicoses are rare these days due to commercially available high-quality diets; however, poorly stored diets, inadequate husbandry of exotic pets, or problems in a farm animal environment may result in zinc, vitamin A, vitamin C, and fatty acid, or copper deficiency. Inherited deficiencies due to abnormal zinc absorption through the gastrointestinal tract must be considered in Nordic breed dogs and goats., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Cytokine and antiangiogenic gene therapies have proved effective in implanted hepatocellular carcinoma (HCC) models in which small tumor burdens were established in small rodents. These models, however, may not reflect human HCCs, which are frequently detected at a stage when tumors are large and multifocal. In addition, HCC in patients is often associated with viral hepatitis. To investigate the effectiveness of a mixture type of gene therapy strategy on large tumor burdens, we used the woodchuck model in which woodchuck hepatitis virus-induced HCCs are large and multifocal, simulating the conditions in humans. Adenoviruses encoding antiangiogenic factors (pigment epithelium-derived factor and endostatin) or cytokines (GM-CSF and IL-12) were delivered via the hepatic artery separately or in combination into woodchuck livers bearing HCCs. Our results showed that the mixture type of strategy, which contained two cytokines and two antiangiogenic factors, had better antitumor effects on large tumors as compared with monotherapy either with antiangiogenic or cytokine genes. The immunotherapy recruited significant levels of CD3(+) T cells that infiltrated the tumors, whereas the antiangiogenesis-based therapy significantly reduced tumor vasculature. The mixture type of gene therapy achieved both effects. In addition, it induced high levels of natural killer cells and apoptotic cells and reduced the levels of immunosuppressive effectors in the tumor regions. Hence, antiangiogenic therapy may provide the advantage of reducing immune tolerance in large tumors, making them more vulnerable to the immune reactions. Our study implies that in the future, the combination therapy may prove effective for the treatment of patients with advanced HCC.

We and others frequently have noted serum potassium levels of 8.0 +/- 0.85 mEq/L or greater in laboratory mice; this concentration has even been published as the upper limit of a 'normal' reference range. However, if bone fide, this potassium concentration would be incompatible with life in all species. We investigated conditions frequently encountered in the research setting to distinguish artifactual from true hyperkalemia. Variables evaluated included site of collection, time allowed for clot formation before serum separation, time elapsed between collection and analysis of samples collected in a serum separator tube, precollection method of anesthesia, and euthanasia technique. Serum potassium was measured from 75 C57BL/6NTac 10-wk-old female mice and divided into at least 5 mice per variable. Animals were euthanized by exsanguination immediately after terminal CO₂ or ketamine-xylazine (KX) administration. Mice euthanized with CO₂ had higher mean serum potassium (7.0 +/- 0.5 mEq/L) and range serum potassium (6.0 to 8.1 mEq/L) than did KX-treated mice. CO₂ inhalation resulted in significantly lower blood pH (6.9 +/- 0.1), higher pCO₂ (153.3 +/- 38.8 mm Hg), and higher lactate levels (3.9 +/- 0.9 mmol/L) than did KX anesthesia followed by exsanguination. These results suggest that antemortem respiratory acidosis from CO₂ administration causes artifactual hyperkalemia in mice. Therefore, blood collection under KX anesthesia is preferable over CO₂ inhalation to obtain accurate potassium values from mice.

A 1.5-yr-old captive male Gambian giant pouched rat (Cricetomys gambianus) died after suffering from anorexia, weakness, and dyspnea for 3 wk. Thoracic radiographs of thorax and abdomen and computed tomography showed a severe biventricular enlargement of the heart and a moderate hepatomegaly. Necropsy revealed a severe, bilateral hypertrophic cardiomyopathy and dilation of the right ventricle due to multifocal bilateral, valvular endocardiosis of all atrioventricular valves and acute hepatic congestion. Histologically, the atrioventricular valves were multifocally thickened by a marked endocardiosis with stromal accumulation of Periodic acid-Schiff (PAS)-positive, mucinous material. Although common in dogs, endocardiosis has not been described in Nesomyidaes. As in other affected species, the pathogenesis of endocardiosis in this species remains unclear.

Insufficient wear of rodent incisors often results in malocclusion and rapid tooth elongation. This condition may go undetected for a prolonged time and have a negative effect on affected animals' welfare. Dental overgrowth can lead to undernutrition due to chronic difficulty in feeding and may cause trauma to the surrounding tissues, potentially ultimately resulting in death. Here we describe the increased incidence of malocclusion observed during a longitudinal study of the normal growth and aging of Wistar rats. Histologic examination of the temporomandibular joint of affected animals did not reveal any inflammatory or degenerative changes. Because no environmental factor could be implicated in the condition, we considered that aging or genetic factors were responsible for its appearance. We conclude that special attention should be given to the potential appearance of malocclusion during long-term rodent studies, because its incidence may adversely affect the animals' health and general wellbeing.

Guinea pigs and chinchillas, which have become increasingly popular pets, are today more commonly presented as adult and geriatric animals. Problems of older guinea pigs and chinchillas include those related to diet and management, infections whose symptoms are more common in older animals, and neoplasia., (Copyright 2010. Published by Elsevier Inc.)

This case report describes the unanticipated development of pyometra in Brown Norway rats after treatment with estrogen. Sprague Dawley and Brown Norway rats were ovariectomized and randomly assigned to treatment groups (subcutaneous implantation of either a capsule containing 20 mg 17beta-estradiol or an empty capsule, as a control). After irradiation of only the right eye, the rats were followed for several months in an attempt to determine the effects of estrogen on radiation cataractogenesis and investigate potential strain differences in this phenomenon. However, all Brown Norway rats that received estradiol treatment developed pyometra, whereas none the Sprague Dawley or control Brown Norway rats did. This case demonstrates the potential adverse effects of exogenous estrogen therapy, which are strain-specific in the rat. Caution should be taken when designing estrogen-related experiments involving Brown Norway rats and other potentially sensitive strains.

Spontaneous tumors are reported to occur in 45% to 71% of Sprague-Dawley rats, yet few studies have considered the effect of the sedentary condition of standard laboratory cages on tumorigenesis. Tumor profiles and tumor promoting hormone prolactin were compared in female Sprague-Dawley rats (108) that were allocated into 3 groups: those housed without outside activity (SED group), with twice-weekly 1-h sessions of physical activity in large box (PA group), and with regular voluntary running-wheel exercise (EX). Compared with the EX group, SED rats had more and larger tumors throughout most of their lifespan; tumor profiles of PA rats were similar to those of the SED group. A larger percentage of animals in the SED group had tumors (54%), compared with EX rats (38%). At 64 wk, tumors in SED animals included thyroid carcinoma, malignancy, mammary fibroadenoma, cystadenoma, and granuloma, whereas benign mammary gland cysts were most common in EX. Prolactin levels were highest in SED animals at 24 and 52 wk. In conclusion, increased tumor number, increased tumor size, type of spontaneous tumor, and increased prolactin in rats were associated with standard laboratory housing, which limited physical activity, and were not primarily due to aging.

Male and female mice were anesthetized by intraperitoneal injection with a mixture delivering 0.5 mg/kg medetomidine and 50 mg/kg ketamine to achieve immobilization for whole-body radiographs and bone densitometry, as part of a phenotypic screen for bone and mineral disorders in mice carrying genetic modifications induced through mutagenesis with N'-ethyl-N'-nitrosourea. Morbidity and mortality occurred in 19 of 628 (3%) of male mice 24 to 72 h after a seemingly uneventful recovery from anesthesia. No morbidity or mortality occurred in 1564 female mice that were similar in age to the affected male mice and that underwent the same procedure. Of the 7 male mice that underwent postmortem examinations, 5 had urinary bladders grossly distended with urine and 1 had ascites. In addition, the pelvic or penile urethra in 5 of the examined male mice was obstructed with seminal coagulum associated with varying degrees of erosion of the urothelial lining and inflammation of the urethra. In 2 of these animals, from which plasma samples were recovered, azotemia, hyperphosphatemia, and hyperkalemia were present. The predilection for delayed morbidity and mortality in males after anesthesia suggests that anesthesia with 0.5 mg/kg medetomidine and 50 mg/kg ketamine is a potential risk factor for obstructive uropathy due to release of seminal coagulum. This adverse effect did not recur when we altered our anesthesia protocol to 10 mg/kg xylazine and 100 mg/kg ketamine.

Bone marrow transplantation (BMT) is the treatment of choice for many leukemias, solid tumors, and metabolic diseases. The field of bone marrow research is highly dependent on in vivo experimentation, because in vitro techniques do not mimic these complicated in vivo systems. Therefore, understanding the medical and husbandry care needs of these transiently immunodeficient bone marrow recipient animals is crucial for researchers, veterinary and animal care personnel. Here we discuss the principles of bone marrow transplantation, mouse pathogens that can interfere with transplantation research, and important husbandry and veterinary practices for mice that may help to minimize unnecessary infections during the transplantation process. Whole-body irradiation is one of the most common tools for myeloablation of the recipient's bone marrow. We discuss the crucial role of the irradiator for BMT research and the importance of aseptic husbandry practices to lessen the possibility of the irradiator for being a source for disease transmission. Finally, we discuss some important guidelines for Institutional Animal Use and Care Committees reviewing irradiation and BMT protocols.

Objective: Although the detrimental physical health effects of social isolation have been known for three decades, the answers to how and why social relationships generally improve health remain elusive. Social relationships are not always beneficial, and we examined a structural dimension that may bring about their salubrious effects: affiliative reciprocity during a stressor., Methods: In a lifespan study, female rats lived with their sisters and were tested for temperament, affiliative reciprocity during an everyday stressor at puberty, corticosterone response to a stressor, mammary tumor development and diagnosis, and death., Results: Rats that affiliated more reciprocally during a mild group stressor survived longer (p = .0005), having exhibited a lower corticosterone peak in response to an acute novel stressor in late adulthood (p = .0015), and longer time to the development of spontaneous mammary tumors (p = .02). These effects could not be explained solely by the number of affiliative interactions or individual temperament. Indeed, affiliative reciprocity and neophobia were independent and predicted mortality additively (p = .0002)., Conclusions: Affiliative reciprocity during a stressor, a structural quality of social interactions, protected females from early mammary tumor development (the primary pathology in Sprague-Dawley rats) and early all-cause mortality. Conversely, lack of reciprocity (whether disproportionately seeking or receiving attempted affiliation) was as potent a risk factor as neophobia. Thus a social role increased risk additively with individual temperament. Our data indicate that affiliative reciprocity functions as a buffer for everyday stressors and are likely mediated by attenuated reactivity of the hypothalamic-pituitary-adrenal axis.

An adult intact male guinea pig (Cavia porcellus) was presented with gastrointestinal stasis. Radiographic findings demonstrated a gas- and fluid-filled cecum. Treatment was initiated but the animal died shortly after presentation. Gross postmortem revealed omental torsion with vascular thrombosis and necrosis. This is the first report of omental torsion with vascular thrombosis in a domestic animal.

Two captive agoutis (Dasyprocta mexicana) died of anemia with centrilobular hepatocellular necrosis (2/2), severe flea ectoparasitism (2/2), and cardiomegaly attributed to anemia (1/2). Other agoutis were similarly parasitized and one had anemia. Fleas were manually removed and all agoutis treated topically with propoxur and selamectin and moved to another enclosure. No additional cases of fatal anemia were seen. Cutaneous lesions suggestive of hypersensitivity were observed in three additional agoutis with dorsal alopecia (3/3), a penetrating wound associated with pruritus and self-mutilation in the flank (2/3), flea ectoparasitism at the time of morphologic diagnosis (1/3), and hyperplastic perivascular dermatitis (3/3). One of these died of bacterial infection of the wound. Similar but milder skin disease was seen in 3 out of over 30 maras (Dolichotis patagonum) housed in the same exhibit. Fleas collected from all the fatal agouti cases and maras were classified in the genus Echidnophaga based on the angular front margin of head, contracted thorax, absence of genal and pronotal combs, and the fact that fleas did not jump. These findings suggest that flea ectoparasitism may be an important cause of morbidity and mortality in captive rodents.

Social environment can represent a major source of stress affecting cortisol and/or corticosterone levels, thereby altering the immune response. We have investigated the effects of social isolation on the development of Trypanosoma cruzi infection in female Calomys callosus, a natural reservoir of this protozoan parasite. Animals were divided in groups of five animals each. The animals of one group were kept together in a single cage. In a second group, four females were kept together in a cage with one male. In the final group, five individuals were kept isolated in private cages. The isolated animals showed body weight reduction, decreased numbers of peritoneal macrophages, lower global leucocytes counts, smaller lytic antibody percentage and a significantly higher level of blood parasites compared to the other animals. Their behavior was also altered. They were more aggressive than grouped females, or females exposed to the presence of a male. These results suggest that isolation creates a distinct social behavior in which immunity is impaired and pathogenesis is enhanced.

A total of 835 rodents captured in Beijing, China, were tested for hantavirus infection. Fifty-five (6.6%) were positive for viral RNA when lung tissue samples were examined by reverse transcriptase-polymerase chain reaction. Of 666 sera collected from the above rodents, 50 (7.5%) were positive for IgG antibody by ELISA. Among the 50 seropositive rodents, 37 were positive for viral RNA. In addition, five rodents were positive for viral RNA but negative for IgG antibody. The infection rates among study sites (chi(2) = 28.93, df = 8, P = 0.001) and habitats (chi(2) = 22.88,df = 7, P = 0.02) were significantly different. The sequences of partial M-segment of hantaviruses detected in 11 representative rodents had 0.1-8.2% divergence. Phylogenetic analysis showed that our hantavirus sequences fell into three different lineages regardless of geographical origin or rodent species. A strain detected from a trading center of agricultural products, which might be imported from other provinces, was genetically different from other strains of Beijing.

The frequency of documented endocrine diseases in rodents and other small mammals varies considerably among the species maintained as pets, biomedical research animals, or display animals in zoos. The clinical diagnosis of endocrine diseases almost never occurs in free-ranging animals in their native habitat. Feral animals that have clinical endocrine disease, such as neoplasia, adrenal cortical hyperplasia, or diabetes, would exhibit clinical signs of altered behavior that would result in their removal by predators. The diagnosis of endocrine disease thus takes place in the relatively protective environment of captivity. This observation should forewarn pet owners and clinicians caring for these animals that the environment contributes to the development of endocrine diseases in these animals.

Brown Norway (BN) rats have been found to develop granulomatous pneumonia with high spontaneous incidence under normal husbandry conditions. In our laboratory, ambient particles from the animal housing environment were suspected to be involved in the pathogenesis of these pulmonary lesions. In the present study, we correlated the histopathology of spontaneous granulomatous pneumonia with the cytology of bronchoalveolar lavage fluid (BALF) analysis and animal room particle counts. The results show that the sum of the macroscopic lesion score in the lung correlated with the number of eosinophils in the BALF. Microscopically, the severity of granulomatous lesions was significantly correlated with both pulmonary eosinophils and the number of eosinophils in the BALF, but not with those of neutrophils or lymphocytes. In addition, the histological features of the lesions were not influenced by housing conditions or sensitization with ovalbumin. Ambient particles (0.3-1.0 microm in diameter) in the animal room environment were measured and compared with the number of eosinophils in BALF. Interestingly, there was a significant correlation between them, suggesting a possible relationship between environmental particles and the pathogenesis of granulomatous pneumonia in BN rats. However, further study is needed to clarify the pathogenic mechanism.

Background: It has recently been shown that Ljungan virus (LV) is associated with disease in its wild rodent reservoir. In addition, it has been demonstrated that LV causes malformations and perinatal death in a mouse model. The question was therefore raised whether LV is a zoonotic agent in humans., Methods: Population fluctuations of native rodents in Sweden were compared to the incidence of intrauterine fetal deaths (IUFDs) using the Swedish national hospitalization database. Formalin-fixed tissues from cases of IUFD were investigated using LV-specific immunohistochemistry., Results: Variation in the incidence of IUFDs closely tracked the fluctuations in native rodent populations. LV was detected in the brain tissue in 4 of 10 cases of IUFDs investigated by immunochemistry. LV was also detected in the placenta in 5 of the 10 IUFD cases, but in none of 20 placentas from normal pregnancies., Conclusions: LV may play an important role in IUFDs.

Under specific pathogen-free conditions, 1.3% to 1.8% of litters born in our inbred 101/H and C3HeB/FeJ mouse colonies had pups with steatorrhea and runting. Clinically affected male and female pups were first identified when they were from 14 to 25 d old. Unaffected littermates were healthy and were weaned successfully. Postmortem findings in 8 clinically affected mice included a small, poorly differentiated exocrine pancreas comprising cytokeratin-negative duct-like structures but lacking recognizable acinar cells with their normal carboxypeptidase B-positive zymogen granules. Endocrine pancreas islets were unremarkable and contained insulin-positive beta cells and glucagon-positive alpha cells. There was mild inflammation of the hindgut but no evidence of intestinal pathogens or marked inflammation or necrosis of pancreas, either alone or as part of a multisystemic inflammatory condition. Sera from pups in 4 affected litters did not contain antibodies to reovirus 3, mouse coronavirus, rotavirus, or mouse adenovirus 2. Furthermore, 4 sets of parental mice and sentinel mice from the facility were negative for 13 viruses, bacteria, and parasites. C3HeB/FeJ and 101/H inbred strains may be genetically predisposed because the steatorrhea and runting was absent in 13 other mouse strains and subspecies bred in the specific pathogen-free facility. This condition resembles exocrine pancreas hypoplasia, but the inheritance is complex. A wider implication is that runting coupled with steatorrhea are phenotypic criteria to suspect pancreatic disease that could be used in the context of a mouse N-ethyl-N-nitrosourea-mutagenesis program to identify potential mutants with defects in pancreas development.