Project description:Sodium appetite is an instinct that involves avid specific intention. It is elicited by sodium deficiency, stress-evoked ACTH and by reproduction. Genome-wide microarrays in sodium deficient mice, or following ACTH infusion, showed upregulation of hypothalamic genes, including DARPP-32, dopamine receptors-1 and -2, alpha-2C-adrenoceptor, and STEP. Both DARPP-32 and neural plasticity regulator, ARC were upregulated in lateral hypothalamic orexinergic neurons by sodium deficiency. Administration of dopamine D1- (SCH23390) and D2-receptor (raclopride) antagonists reduced gratification of sodium appetite triggered by sodium deficiency. SCH23390 was specific, having no effect on osmotic-induced water drinking, whereas raclopride also reduced water intake. D1-receptor knockout mice had normal sodium appetite, indicating compensatory regulation. It was insensitive to SCH23390, confirming the absence of off-target effects. Bilateral microinjection of SCH23390 (100nM in 200nL) into rats? lateral hypothalamus greatly reduced sodium appetite. Gene Set Enrichment Analysis in hypothalami of mice with sodium appetite showed significant enrichment of gene sets previously linked to addiction (opiates, cocaine). This finding of concerted gene regulation was attenuated upon gratification with perplexingly rapid kinetics of only 10 minutes, anteceding significant absorption of salt from the gut. Salt appetite and hedonic liking of salt taste have evolved over more than a hundred million years e.g. being present in Metatheria. Drugs causing pleasure and addiction are comparatively recent and likely reflect usurping of evolutionary ancient systems with high survival value by the gratification of contemporary hedonic indulgences. Our findings outline a novel molecular logic for instinctive behavior encoded by the brain with possible important translational-medical implications. Transcripts were profiled in the hypothalamus and whole brain of control and salt craving animals to determine the gene expression profile corresponding to that behavioral state. We show an over-representation of addiction-related genes in the set that is common to different methods of salt craving. Mouse hypothalamus and whole brain under three conditions: control, furosemide treated, and ACTH treated. 4 or 5 biological replicated per group. Two channels - experimental and reference are used.
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: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.
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.