Project description:Cardiac-specific PPARalpha transgenic (Tg-PPARalpha) mice show mild cardiac hypertrophy and systolic dysfunction. The failing heart phenotypes observed in Tg-PPARalpha are exacerbated by crossing with cardiac-specific Sirt1 transgenic (Tg-Sirt1) mice, whereas Tg-Sirt1 mice themselves do not show any cardiac hypertrophy or systolic dysfunction. To investigate the mechanism leading to the failing heart phenotypes in TgPPARalpha/Tg-Sirt1 bigenic mice, microarray analyses were performed. The microarray analyses revealed that many ERR target genes were downregulated in Tg-PPARalpha and in Tg-Sirt1, and they were further downregulated in the Tg-PPARalpha/Tg-Sirt1 bigenic mice.
Project description:Cardiac-specific PPARalpha transgenic (Tg-PPARalpha) mice show mild cardiac hypertrophy and systolic dysfunction. The failing heart phenotypes observed in Tg-PPARalpha are exacerbated by crossing with cardiac-specific Sirt1 transgenic (Tg-Sirt1) mice, whereas Tg-Sirt1 mice themselves do not show any cardiac hypertrophy or systolic dysfunction. To investigate the mechanism leading to the failing heart phenotypes in TgPPARalpha/Tg-Sirt1 bigenic mice, microarray analyses were performed. The microarray analyses revealed that many ERR target genes were downregulated in Tg-PPARalpha and in Tg-Sirt1, and they were further downregulated in the Tg-PPARalpha/Tg-Sirt1 bigenic mice. Four groups of cardiac-specific transgenic mice were used for the study, i.e., control, PPARalpha, Sirt1 and PPARalpha/Sirt1. Hearts were dissected after 10-11 weeks of male FVB background transgenic mice. Total RNA was prepared from the hearts to conduct the microarray analyses.
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.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
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: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 ‘hotspots,’ 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 ‘fertile’ 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.