Project description:Fgf18 gene is strongly expressed in hair follicles of mouse dorsal skin during regressing (catagen) and resting (telogen) phases of hair cycle, but not in growth (anagen) phase. This study aims at identifying the function of Fgf18 in the regulation of hair cycle. To define target genes of Fgf18 during telogen phase of hair cycle, we generated mice in which Fgf18 gene is conditionally knocked out in keratin 5-positive epithelial cells (referred to as Fgf18 cKO below). We carried out microarray experiments with mouse back skin samples harboring telogen hair follicles obtained from three 42-d-old Fgf18 cKO male mice, or from three 42-d-old C57BL/6 male mice as control. Total RNA was isolated from each mouse and further purified to polyA RNA using oligo dT30 columns. The RNA samples were pooled for each group. Gene expression was analyzed by one-color analysis using duplicate arrays for each group.
Project description:Fgf18 gene is strongly expressed in hair follicles of mouse dorsal skin during regressing (catagen) and resting (telogen) phases of hair cycle, but not in growth (anagen) phase. This study aims at identifying the effects of FGF18 local delivery on the anagen phase of hair cycle. To define genes affected by local delivery of FGF18 during anagen phase of hair cycle, we injected FGF18 protein subcutaneously into back skin of C3H/HeN mice on day 4 of depilation-induced anagen. As control PBS was injected in place of FGF18. After 24 h (61-d-old), total RNA was isolated from the back skin and purified to poly A RNA. The RNA samples were pooled for each group. Gene expression was analyzed by one-color analysis using single array for each group.
Project description:Fgf18 gene is strongly expressed in hair follicles of mouse dorsal skin during regressing (catagen) and resting (telogen) phases of hair cycle, but not in growth (anagen) phase. This study aims at identifying the function of Fgf18 in the regulation of hair cycle.
Project description:Fgf18 gene is strongly expressed in hair follicles of mouse dorsal skin during regressing (catagen) and resting (telogen) phases of hair cycle, but not in growth (anagen) phase. This study aims at identifying the effects of FGF18 local delivery on the anagen phase of hair cycle.
Project description:Telogen (resting phase) hair follicles are more radioresistant than anagen (growth phase) ones. Irradiation of BALB/c mice in the anagen phase with γ-rays at 6 Gy induced hair follicle dystrophy, whereas irradiation in the telogen phase induced the arrest of hair follicle elongation without any dystrophy after post-irradiation depilation. In contrast, FGF18 was highly expressed in the telogen hair follicles to maintain the telogen phase and also the quiescence of hair follicle stem cells. Therefore, the inhibition of FGF receptor signaling at telogen induced the dystrophy after post-irradiation depilation. In addition, the administration of recombinant FGF18 suppressed cell proliferation in the hair follicles and enhanced the repair of radiation-induced DNA damage, so FGF18 protected the anagen hair follicles against radiation damage to enhance hair regeneration. Moreover, FGF18 reduced the expression of cyclin B1 and cdc2 in the skin and FGF18 signaling induced G2/M arrest in the keratinocyte cell line HaCaT, although no obvious change of the expression of DNA repair genes was detected by DNA microarray analysis. These findings suggest that FGF18 signaling for the hair cycle resting phase causes radioresistance in telogen hair follicles by arresting the proliferation of hair follicle cells.
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: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:BackgroundCopy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.ResultsWe found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR).ConclusionThe analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies.