Project description:We sequenced mRNA from mouse E14.5 embryonic cortex to compare gene expression level and alternative splicing events between 2 control (WT) and 2 Qk cKO. A set of tissue specific splicing factors are thought to govern alternative splicing events during neural progenitors (NPC) to neuron transition by regulating neuron specific exons. Here we proposed one such a factor, RNA-binding protein Qki5, which is specifically expressed in neural stem cells. We performed mRNAseq analysis by using mRNAs obtained from developing cerebral cortices in Qk conditional knockout (cKO) mice. Expectedly, we found huge numbers of alternative splicing changes between control and conditional knock-out relative to that of transcripts level changes. Furthermore, DAVID and Meta-scape analysis revealed that affected spliced genes are involved in axon-development and microtubule-based process. Among these, Ninein protein coding mRNA is listed as a Qk protein dependent alternative splicing targets. Interestingly, this exon encodes very long poly-peptides (2,121 nt) and is known as a previously defined dynamic RNA switch during NPC-to-neuron transition. In addition, we validated that the regulation of this large exon is consistent with Qki5 dependent alternative exon inclusion mode obtained from our previous Qki5 HITS-CLIP analysis. Together Qki5 will add to a list factor of alternative splicing in NPC-to-neuron transition.
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:SILAC based protein correlation profiling using size exclusion of protein complexes derived from seven Mus musculus tissues (Heart, Brain, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
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.