Project description:We performed RNaseq of liver, hypothalamus and vomeronasal organ crosses between inbred stains of M. m. domesticus (strain WSB/EiJ) and M. m. musculus (PWD/PhJ). We also sequenced RNA from the same tissues from parental M. m. musculus (PWD/PhJ).
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven M-bM-^@M-^Xhotspots,M-bM-^@M-^Y seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a M-bM-^@M-^XfertileM-bM-^@M-^Y subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. Gene expression was measured in whole testis in males aged 70(M-BM-15) days. Samples include 294 WSB/EiJ x PWD/PhJ F2s, 11 PWD/PhJ x WSB/EiJ F2s, 8 WSB/EiJ, 8 PWD/PhJ, 6 PWD/PhJ x WSB/EiJ F1s and 4 WSB/EiJ x PWD/PhJ F1s.
Project description:We used a reciprocal cross of Mus musculus and M. domesticus in which F1 males are sterile in one direction and fertile in the other direction, in order to associate expression differences with sterility. Four different crosses were performed. A cross between two strains within each mouse species (M. musculus, PWK/PhJ and CZECHII/EiJ; M. domesticus, LEWES/EiJ and WSB/EiJ). And two reciprocal crosses between a domesticus (LEWES/EiJ) and a musculus (PWK/PhJ) strain. The cross between a musculus female and a domesticus male produces sterile male offspring - whereas all other crosses produced fertile male offspring. Testis tissue from three male mice (60 days old) from all four crosses were analysed on the Affymetrix MG 430.2. Array.
Project description:We compared gene expression differences in the polytypic species complex Mus musculus (Mus musculus musculus, Mus musculus domesticus, Mus musculus castaneus and Mus musculus ssp) with that of Mus spretus via oligonucleotide microarrays representing more than 20,000 genes. Analysis of the results by two way ANOVA statistics suggests that the most genes with significant differences in expression levels among the subspecies are found in liver and kidney and the least in testis. This picture is different when one compares with Mus spretus, where the largest number of differences is found in testis. Keywords: multi-species comparison
Project description:One of the reproductive isolation mechanisms that restricts gene exchange and make speciation irreversible is sterility of inter(sub)specific hybrids. In the Prdm9-driven sterility of Mus m. musculus x Mus m. domesticus hybrids a Prdm9-interacting hybrid sterility gene was mapped in the X-linked Hstx2 locus. Here we show that the Mir465 microRNA gene cluster is the predicted Hstx2 hybrid sterility factor involved in Prdm9 interaction.
Project description:One of the reproductive isolation mechanisms that restricts gene exchange and make speciation irreversible is sterility of inter(sub)specific hybrids. In the Prdm9-driven sterility of Mus m. musculus x Mus m. domesticus hybrids a Prdm9-interacting hybrid sterility gene was mapped in the X-linked Hstx2 locus. Here we show that the Mir465 microRNA gene cluster is the predicted Hstx2 hybrid sterility factor involved in Prdm9 interaction.
Project description:This is the proteomics component of a multi-omics analysis of the aging murine retina. Age is a critical risk factor for vision-threatening retinopathies. Susceptibility to age-related retinal neurodegeneration is genetically influenced, however, no studies have addressed molecular retinal aging signatures across genetically diverse populations. Here, we profile retinal proteomics in an array of genetically diverse mice with age. Proteomics were employed to profile retinal aging signatures in C57BL/6J (B6), 129S1/SvImJ, NZO/HlLtJ (NZO), WSB/EiJ (WSB), CAST/EiJ, PWK/PhJ, NOD/ShiLtJ, A/J, and BALB/cJ mouse strains at 4, 12, and 18M. These data were collated into a publicly available resource.
Project description:We compared gene expression differences in the polytypic species complex Mus musculus (Mus musculus musculus, Mus musculus domesticus, Mus musculus castaneus and Mus musculus ssp) with that of Mus spretus via oligonucleotide microarrays representing more than 20,000 genes. Analysis of the results by two way ANOVA statistics suggests that the most genes with significant differences in expression levels among the subspecies are found in liver and kidney and the least in testis. This picture is different when one compares with Mus spretus, where the largest number of differences is found in testis. The design we employed is a reference design. All tissues were hybridized against a pool of that same tissue from 9 C57BL6 mice. All mice were roughly 12 weeks of age. To control for biological variation, we have used several individual males from each sub-species. RNA was isolated from three different organs, namely brain, liver/kidney and testis.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility. Gene expression was measured in whole testis from males aged 62-86 days. Samples include 190 first generation lab-bred male offspring of wild-caught mice from the Mus musculus musculus - M. m. domesticus hybrid zone.
Project description:Classical laboratory strains show limited genetic diversity and do not harness natural genetic variation. Mouse models relevant to Alzheimer’s disease (AD) have largely been developed using these classical laboratory strains, such as C57BL/6J (B6), and this has likely contributed to the failure of translation of findings from mice to the clinic. Therefore, here we test the potential for natural genetic variation to enhance the translatability of AD mouse models. Two widely used AD-relevant transgenes, APPswe and PS1de9 (APP/PS1), were backcrossed from B6 to three wild-derived strains CAST/EiJ, WSB/EiJ, PWK/PhJ, representative of three Mus musculus subspecies. These new AD strains were characterized using metabolic, functional, neuropathological and transcriptional assays. Strain-, sex- and genotype-specific differences were observed in cognitive ability, neurodegeneration, plaque load, cerebrovascular health and cerebral amyloid angiopathy. Analyses of brain transcriptional data showed strain was the greatest driver of variation. We identified significant variation in myeloid cell numbers in wild type mice of different strains as well as significant differences in plaque-associated myeloid responses in APP/PS1 mice between the strains. Collectively, these data support the use of wild-derived strains to better model the complexity of human AD.