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We created a volumetric template of the marmoset (Callithrix jacchus) brain, which enables localization of the cortical areas defined in the Paxinos et al. (The marmoset brain in stereotaxic coordinates. Elsevier Academic Press, Cambridge, 2012) marmoset brain atlas, as well as seven broader cortical regions (occipital, temporal, parietal, prefrontal, motor, limbic, insular), different brain compartments (white matter, gray matter, cerebro-spinal fluid including ventricular spaces), and various other structures (brain stem, cerebellum, olfactory bulb, hippocampus). The template was designed from T1-weighted MR images acquired using a 3 T MRI scanner. It was based on a single fully segmented marmoset brain image, which was transported onto the mean of 13 adult marmoset brain images using a diffeomorphic strategy that fully preserves the brain topology. In addition, we offer an automatic segmentation pipeline which fully exploits the proposed template. The segmentation pipeline was quantitatively assessed by comparing the results of manual and automated segmentations. An associated program, written in Python, can be used from a command-line interface, or used interactively as a module of the 3DSlicer software. This program can be applied to the analysis of multimodal images, to map specific cortical areas in lesions or to define the seeds for further tractography analyses.

[EN] Rabbit haemorrhagic disease (RHD) is a critical health threat to the rabbit industry in Europe. In 2018, the French rabbit industry adopted a voluntary control plan against this disease. In this context, two epidemiological studies were conducted on RHD outbreaks that occurred between 2013 and 2018 in France. The objectives were to describe the spread of RHD due to the new genotype RHDV GI.2 (rabbit haemorrhagic disease virus GI.2) and to identify rearing factors influencing the occurrence of the disease in order to guide the prevention measures recommended in the control plan. An analysis of cases on 295 farms between 2013 and 2017 showed that 32% of farms were affected at least once; the incidence of the disease increased in 2016-2017 compared to 2013-2015. Farms already affected in 2013-2015 had a higher risk of being infected in 2016-2017 than those that remained unaffected until 2015 (Relative Risk and 95% Confident Interval 1.7 [1.1-2.7]). A case-control study carried out between 2016 and 2018 on 37 outbreaks and 32 control farms revealed variability in biosecurity and decontamination practices between farms. The risk of being infected tends to be linked to these practices, but certain structural factors (e.g. the manure disposal system, transfer of rabbits at weaning) could also influence the risk of virus introduction into farms. In the context of a limited vaccination coverage of the farms (only females are vaccinated), these hypotheses will be studied further, using information from the RHD outbreak monitoring system implemented at the same time as the control plan in 2018., This study was founded by the French Ministry of Agriculture (2017-430 / 170274).

Tractography, a noninvasive technique tracing brain pathways from diffusion tensor magnetic resonance imaging (DTI) data, is increasingly being used for brain investigation of domestic mammals. In the equine species, such a technique could be useful to improve our knowledge about structural connectivity or to assess structural changes of white matter tracts potentially associated with neurodegenerative diseases. The goals of the present study were to establish the feasibility of DTI tractography in the equine brain and to provide a morphologic description of the most representative tracts in this species. Postmortem DTI and susceptibility-weighted imaging (SWI) of an equine brain were acquired with a 3-T system using a head coil. Association, commissural, and projection fibers, the three fiber groups typically investigated in tractography studies, were successfully reconstructed and overlaid on SWI or fractional anisotropy maps. The fibers derived from DTI correlate well with their description in anatomical textbooks. Our results demonstrate the feasibility of using postmortem DTI data to reconstruct the main white matter tracts of the equine brain. Further DTI acquisitions and corresponding dissections of equine brains will be necessary to validate these findings and create an equine stereotaxic white matter atlas that could be used in future neuroimaging research.

Saltatorial locomotion is a type of gait based on hopping that in mammals can be found in rabbits, hares, kangaroos, and some species of rodents. The molecular mechanisms that control and fine tune the formation of this type of gait are unknown. Here, we take advantage of one breed of domesticated rabbits, the sauteur d’Alfort, that exhibits an abnormal locomotion behavior characterized by the loss of the typical jumping that characterizes wild-type rabbits. Strikingly, individuals from this breed frequently adopt a bipedal gait using their front legs. Using a combination of experimental crosses and whole genome sequencing, we show that a single locus containing the RAR related orphan receptor B gene (RORB) explains the atypical gait of these rabbits. We found that a splice-site mutation in an evolutionary conserved site of RORB results in several aberrant transcript isoforms incorporating intronic sequence. This mutation leads to a drastic reduction of RORB-positive neurons in the spinal cord, as well as defects in differentiation of the DMRT3-expressing population of interneurons. Our results demonstrate that RORB plays an important role in neuronal differentiation of the rabbit spinal cord that is required for normal saltatorial locomotion. They further suggest that the DMRT3 gene appears to have a general role in regulating gait across species and different types of locomotion.

Saltatorial locomotion is a type of hopping gait that in mammals can be found in rabbits, hares, kangaroos, and some species of rodents. The molecular mechanisms that control and fine-tune the formation of this type of gait are unknown. Here, we take advantage of one strain of domesticated rabbits, the sauteur d’Alfort, that exhibits an abnormal locomotion behavior defined by the loss of the typical jumping that characterizes wild-type rabbits. Strikingly, individuals from this strain frequently adopt a bipedal gait using their front legs. Using a combination of experimental crosses and whole genome sequencing, we show that a single locus containing the RAR related orphan receptor B gene (RORB) explains the atypical gait of these rabbits. We found that a splice-site mutation in an evolutionary conserved site of RORB results in several aberrant transcript isoforms incorporating intronic sequence. This mutation leads to a drastic reduction of RORB-positive neurons in the spinal cord, as well as defects in differentiation of populations of spinal cord interneurons. Our results show that RORB function is required for the performance of saltatorial locomotion in rabbits., Author summary Rabbits and hares have a characteristic jumping gait composed of an alternate rhythmical movement of the forelimbs and a synchronous bilateral movement of the hindlimbs. We have now characterized a recessive mutation present in a specific strain of domestic rabbits (sauteur d’Alfort) that disrupts the jumping gait. The mutation causing this defect in locomotion pattern occurs in the gene coding for the transcription factor RORB that is normally expressed in many regions of the nervous system especially in the spinal cord dorsal horn. Our results show that expression of RORB is drastically reduced in the spinal cord of affected rabbits which results in a developmental defect. This study is an advance in our understanding how locomotion is controlled in vertebrates.

Rabbits softly swept to domestication When people domesticate animals, they select for tameness and tolerance of humans. What else do they look for? To identify the selective pressures that led to rabbit domestication, Carneiro et al. sequenced a domestic rabbit genome and compared it to that of its wild brethren (see the Perspective by Lohmueller). Domestication did not involve a single gene changing, but rather many gene alleles changing in frequency between tame and domestic rabbits, known as a soft selective sweep. Many of these alleles have changes that may affect brain development, supporting the idea that tameness involves changes at multiple loci. Science , this issue p. 1074 ; see also p. 1000

The host range of HEV in Europe is expanding, and zoonotic transmission of HEV from rabbits is possible., Hepatitis E virus (HEV) strains from rabbits indicate that these mammals may be a reservoir for HEVs that cause infection in humans. To determine HEV prevalence in rabbits and the strains’ genetic characteristics, we tested bile, liver, and additional samples from farmed and wild rabbits in France. We detected HEV RNA in 7% (14/200) of bile samples from farmed rabbits (in 2009) and in 23% (47/205) of liver samples from wild rabbits (in 2007–2010). Full-length genomic sequences indicated that all rabbit strains belonged to the same clade (nucleotide sequences 72.2%–78.2% identical to HEV genotypes 1–4). Comparison with HEV sequences of human strains and reference sequences identified a human strain closely related to rabbit strain HEV. We found a 93-nt insertion in the X domain of open reading frame 1 of the human strain and all rabbit HEV strains. These findings indicate that the host range of HEV in Europe is expanding and that zoonotic transmission of HEV from rabbits is possible.

International audience; Understanding the genetic structure of domestic species provides a window into the process of domestication and motivates the design of studies aimed at making links between genotype and phenotype. Rabbits exhibit exceptional phenotypic diversity, are of great commercial value, and serve as important animal models in biomedical research. Here, we provide the first comprehensive survey of nucleotide polymorphism and linkage disequilibrium (LD) within and among rabbit breeds. We resequenced 16 genomic regions in population samples of both wild and domestic rabbits and additional 35 fragments in 150 rabbits representing six commonly used breeds. Patterns of genetic variation suggest a single origin of domestication in wild populations from France, supporting historical records that place rabbit domestication in French monasteries. Levels of nucleotide diversity both within and among breeds were ;0.2%, but only 60% of the diversity present in wild populations from France was captured by domestic rabbits. Despite the recent origin of most breeds, levels of population differentiation were high (FST 5 17.9%), but the majority of polymorphisms were shared and thus transferable among breeds. Coalescent simulations suggest that domestication began with a small founding population of less than 1,200 individuals. Taking into account the complex demographic history of domestication with two successive bottlenecks, two loci showed deviations that were consistent with artificial selection, including GPC4, which is known to be associated with growth rates in humans. Levels of diversity were not significantly different between autosomal and X-linked loci, providing no evidence for differential contributions of males and females to the domesticated gene pool. The structure of LD differed substantially within and among breeds. Within breeds, LD extends over large genomic distances. Markers separated by 400 kb typically showed r2 higher than 0.2, and some LD extended up to 3,200 kb. Much less LD was found among breeds. This advantageous LD structure holds great promise for reducing the interval of association in future mapping studies.

Epizootic Rabbit Enteropathy (ERE) is a severe clinical syndrome of rabbits causing high economic losses for farmers. ERE first appeared in France in 1996. A retrospective case–control survey was carried out to identify the risk factors of acute expression of ERE, after weaning, in 96 kindling-to-finish rabbit farms in western France during 2001 and 2002. Farm status was defined according to the expression of clinical signs of ERE and mortality rates in the last five broiler rabbit batches. Comparisons of structural characteristics, rearing conditions and herd management showed that the risk factors for acute ERE expression were late weaning (rabbit age at weaning ≥ 35 days, RR = 4.44, 95% CI [1.36–21.71]), transfer of young rabbits at weaning (young rabbit transfer or combined practice RR = 2.83, 95% CI [1.16–9.33]), and high volume of the fattening room (air volume/rabbit weight in fattening room at weaning ≥ 0.14m 3 /kg, RR = 2.98, 95% CI [1.29–8.42]) and a high mortality rate in young rabbits before weaning (i.e. rate ≥ 10.5%; RR = 2.18, 95% CI [1.20–3.53]).

International audience; Over thousands of years humans changed the genetic and phenotypic composition of several organisms and in the process transformed wild species into domesticated forms. From this close association, domestic animals emerged as important models in biomedical and fundamental research, in addition to their intrinsic economical and cultural value. The domestic rabbit is no exception but few studies have investigated the impact of domestication on its genetic variability. In order to study patterns of genetic structure in domestic rabbits and to quantify the genetic diversity lost with the domestication process, we genotyped 45 microsatellites for 471 individuals belonging to 16 breeds and 13 wild localities. We found that both the initial domestication and the subsequent process of breed formation, when averaged across breeds, culminated in losses of ~20% of genetic diversity present in the ancestral wild population and domestic rabbits as a whole, respectively. Despite the short time elapsed since breed diversification we uncovered a well-defined structure in domestic rabbits where the FST between breeds was 22%. However, we failed to detect deeper levels of structure, probably consequence of a recent and single geographic origin of domestication together with a non-bifurcating process of breed formation, which were often derived from crosses between two or more breeds. Finally, we found evidence for intrabreed stratification that is associated with demographic and selective causes such as formation of strains, colour morphs within the same breed, or country/breeder of origin. These additional layers of population structure within breeds should be taken into account in future mapping studies.

SummaryIn Europe, more than 60 breeds are described by the national associations of rabbit breeders. However, these breeds are scarcely used in the commercial production of rabbit meat in Europe, which is based mainly on commercial strains. A European programme, coordinated by the I. N. R. A., has been initiated to realise the inventory of all these breeds and to evaluate the zootechnical value and the genetic characteristics of some of them. Through the European association of rabbit breeders and the FAO national focal points, all the European countries have been asked to fill out a questionnaire describing their populations of rabbits. A data bank is being set up, which will be included in the FAO (DAD-IS) and EAAP data banks. A sample of 10 breeds has been chosen (Flemish Giant, French Lop, Belgian Hare, Vienna White, Champagne Argente, Thuringer, Fauve de Bourgogne, Chinchilla, Himalayan, British). Their zootechnical value (reproduction, growth and carcass traits) is being evaluated on three experimental farms, in comparison with a control breed. At the same time, their genetic polymorphism and the genetic distances between these 10 breeds are calculated on the basis of microsatellites, mitochondrial DNA, other genetic markers and protein polymorphism. Finally, a bank of frozen embryos from these 10 breeds is being constituted.

Pneumocystis carinii$ is an opportunistic pathogen that causes pneumonia in immunocompromised patients. To investigate the genetic diversity of #P. carinii$ populations, multilocus enzyme electrophoresis was used to analyze five enzyme systems (malate dehydrogenase, glucose phosphate isomerase, leucine aminopeptidase, malic enzyme, and 6-phosphogluconate dehydrogenase). Only five different multilocus associations (zymodemes) were recorded for the 70 isolates studied. While only one multilocus combination was found in mice and rabbits, three different multilocus associations were recorded in rats. Population genetic tests and phylogenetic analysis strongly suggest that #P. carinii$ genotypes are host-specific, in agreement with molecular study results, and that no genetic exchange occurs between genotypes from different host species. This hypothesis could be verified only by the evolutionary genetic approach, which relies here on multilocus analysis. (Résumé d'auteur)

[EN] A study of safety of combined vaccination against myxomatosis and VHD was performed using a duly reconstituted vaccine made of a live homologous myxomatosis component SG33 strain and of an inactivated VHD component in adjuvant AG88 strain. The vaccine was administered intradermally to a representative sample of pet rabbits. A local reaction at the vaccine administration area was frequently observed from 2 to 3 days after vaccination in young animals. These local reactions were less frequently observed in adults. The reaction consisted of a local rash which usually disappeared 2 to 3 days after vaccination (maximum 1 week). The immune response following vaccination was monitored by antibody production against VHD and myxomatosis using, for the VHD vaccine component, an IHA titration method, and, for myxomatosis component, an ELISA titration method. Antibody production after vaccination was observed for both components. Maximum VHD IHA titre (192 ± 130) was obtained in vaccinated animals one month after vaccine administration. Antibodies were still detected in these animals one month later (94 ± 39). Mean titre obtained in unvaccinated controls was equal to 0. Maximum myxomatosis ELISA titre (10518 ± 2417) was obtained two months after vaccine administration. Mean titre obtained at the same time in unvaccinated controls was close to 0 (889 ± 744).

International audience; The reproduction traits of 544 does from eight breeds were evaluated and compared to a control strain (INRA 9077) on three experimental farms, one of which used artificial insemination. The founders came from 110 French, Swiss and Italian breeders. These breeds were the following, in the order of decreasing body weight at amting: Argenté de Champagne, INRA 9077, Thuringer, Vienna White, Fauve de Bourgogne, Belgian Hare, Chinchilla, English and Himalayan. The overall reproductive performances of these eight breeds were lower than the control but differed markedly in the components of productivity. The three small-sized breeds had low prolificacy but good fertility and the survival rate between birth and weaning (within weaned litters) was as high as in the control. The Fauve de Bourgogne and Argenté de Champagne were the most productive among the medium-sized breeds. The least productive breeds were the Belgian Hare, in spite of its good prolificacy, because of the low survival rate of the young rabbits, and the Vienna White, because of poor fertility and the low rate of weaned litters. In spite of its poor fertility, the Thuringer had an intermediate productivity, due to good viability of the young rabbits. The recording of production data on the original farms would make it possible to better understand these results in order to improve them.; Évaluation des performances de reproduction de 8 races de lapin en élevages expérimentaux. Les performances de reproduction de 544 lapines de 8 races ont été évaluées en présence d'une souche témoin (INRA 9077) dans 3 élevages expérimentaux, dont un en insémination artificielle. Les fondateurs provenaient de 110 élevages, français, suisses et italiens. Par ordre décroissant de poids à la saillie, ces races sont : Argenté de Champagne, INRA 9077, Chamois de Thuringe, Blanc de Vienne, Fauve de Bourgogne, Lièvre Belge, Chinchilla, Papillon Anglais et Russe. Ces 8 races ont globalement des performances de reproduction inférieures au témoin, mais diffèrent sensiblement au niveau des composantes de la productivité. Les 3 races de petit format ont une faible prolificité mais une bonne fertilité et un taux de mortalité naissance-sevrage dans les portées sevrées équivalent au témoin. Le Fauve de Bourgogne et l'Argenté de Champagne sont les plus productives des races de format moyen. Les moins productives sont le Lièvre Belge, malgré sa bonne prolificité, à cause de la faible survie des lapereaux, et le Blanc de Vienne, du fait d'une fertilité médiocre et d'un faible taux de sevrage des portées. Malgré sa mauvaise fertilité, le Chamois de Thuringe a une productivité intermédiaire, grâce à la bonne viabilité des lapereaux. Un recueil de données zootechniques chez les éleveurs permettrait de mieux comprendre ces résultats en vue de les améliorer.

WE wish to report the detection of a new variant of rabbit haemorrhagic disease virus (RHDV) (Lagovirus, Caliciviridae) which is circulating in France and has been causing high mortality in domestic and wild rabbit populations since the end of the summer of 2010. Rabbit haemorrhagic disease (RHD)

International audience; Since summer 2010, numerous cases of Rabbit Haemorrhagic Disease (RHD) have been reported in north-western France both in rabbitries, affecting RHD-vaccinated rabbits, and in wild populations. We demonstrate that the aetiological agent was a lagovirus phylogenetically distinct from other lagoviruses and which presents a unique antigenic profile. Experimental results show that the disease differs from RHD in terms of disease duration, mortality rates, higher occurrence of subacute/chronic forms and that partial cross-protection occurs between RHDV and the new RHDV variant, designated RHDV2. These data support the hypothesis that RHDV2 is a new member of the Lagovirus genus. A molecular epidemiology study detected RHDV2 in France a few months before the first recorded cases and revealed that one year after its discovery it had spread throughout the country and had almost replaced RHDV strains. RHDV2 was detected in continental Italy in June 2011, then four months later in Sardinia.