Project description:Deletion of Tbx1, a member of the T-box transcription factor gene family, results in abnormal epithelial fusion between the palatal shelves and the mandible, which induces cleft palate by inhibiting elevation of the palatal shelves. We used microarrays to determine the downstream genes of Tbx1 during palatogenesis and identified distinct classes of dysregulated genes.
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:To assess the influence of Tbx1 on gene expression profile within the developing palate we performed a microarray screen using RNA isolated from dissected secondary palate shelves of E13.5 wild type, Tbx1+/- and Tbx1-/- mice. Significant differences were identified between genotypes, with a total of 67 genes demonstrating at least a 2-fold change (p<0.05) in expression. These were clustered into 5 groups, including those downregulated in mutant compared to wild type and heterozygote (n=36); those progressively downregulated from wild type to mutant (n=12); those upregulated in heterozygote and downregulated in mutant compared to wild type (n=2); those progressively upregulated from wild type to mutant (n=12) and those downregulated in heterozygote and upregulated in mutant compared to wild type (n=5). High-throughput real time quantitative RT-PCR confirmed a total of 18 genes significantly changed between wild type and mutant and 24 between heterozygote and mutant. Amongst these, 15 were present in both groups and all except 1 were downregulated in the mutant. There were no significant differences in gene expression between wild type and heterozygous palatal shelves. Secondary palatal shelf pairs were carefully microdissected from E13.5 Tbx1+/+; Tbx1+/- and Tbx1-/- embryos (3 embryos per genotype as biological replicates). RNA was extracted from each pooled shelf pair generating nine RNA samples in total, each one analysed using a single microarray.
Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.