Mus musculus
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ABSTRACT:
PROVIDER: PRJNA147245 | ENA |
REPOSITORIES: ENA
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Project description:Body temperature is maintained in a narrow range in mammals, primarily controlled by sweating. In humans, the dynamic thermoregulatory organ, comprised of 2-4 million sweat glands distributed over the body, can secrete up to 4 liters of sweat per day1, thereby making it possible to withstand high temperatures and run long distances. The genetic basis for sweat gland function, however, is largely unknown. We find that a forkhead transcription factor, FoxA1, is required to generate mouse sweating capacity. When FoxA1 is ablated, mice are otherwise healthy and sweat gland morphogenesis occurs, but no sweating ensues, with the Nkcc1 sodium/potassium/chloride co-transporter and a specialized Ca2+-activated bicarbonate channel protein, Best2, both sharply down-regulated, and glycoprotein accumulating in gland lumens and ducts. Furthermore, Best2 knockout mice display comparable anhidrosis and glycoprotein accumulation. These findings link earlier observations that both sodium/potassium/chloride exchange and Ca2+ are required for sweat production. FoxA1 is inferred to regulate two corresponding features of sweat secretion. One, via Best2, catalyzes a bicarbonate gradient that could help to drive calcium-associated ionic transport; the other, requiring Nkcc1, facilitates monovalent ion exchange into sweat. These mechanistic components can be pharmaceutical targets to defend against hyperthermia and alleviate defective thermoregulation in the elderly2, and may provide a model relevant to more complex secretory processes. For expression profiling of FoxA1, hairless fore footpad skin (6) was collected from FoxA1 knockouts and wild-type littermates at P10, P14 and P31. Three skin samples from 3 embryos for each genotype at each time point were used for biological replicates. Total RNAs were isolated with Trizol (Invitrogen), precipitated by 7.5M LiCl (Ambion), and cyanine-3-labeled cRNAs were hybridized to the NIA Mouse 44K Microarray v3.0 (Agilent Technologies). Triplicate data were analyzed by ANOVA (6). Genes with FDR<0.05, fold difference>1.5 and mean log intensity>2.0 were considered to be significant.
2012-01-11 | E-GEOD-32347 | biostudies-arrayexpress
Project description:Body temperature is maintained in a narrow range in mammals, primarily controlled by sweating. In humans, the dynamic thermoregulatory organ, comprised of 2-4 million sweat glands distributed over the body, can secrete up to 4 liters of sweat per day1, thereby making it possible to withstand high temperatures and run long distances. The genetic basis for sweat gland function, however, is largely unknown. We find that a forkhead transcription factor, FoxA1, is required to generate mouse sweating capacity. When FoxA1 is ablated, mice are otherwise healthy and sweat gland morphogenesis occurs, but no sweating ensues, with the Nkcc1 sodium/potassium/chloride co-transporter and a specialized Ca2+-activated bicarbonate channel protein, Best2, both sharply down-regulated, and glycoprotein accumulating in gland lumens and ducts. Furthermore, Best2 knockout mice display comparable anhidrosis and glycoprotein accumulation. These findings link earlier observations that both sodium/potassium/chloride exchange and Ca2+ are required for sweat production. FoxA1 is inferred to regulate two corresponding features of sweat secretion. One, via Best2, catalyzes a bicarbonate gradient that could help to drive calcium-associated ionic transport; the other, requiring Nkcc1, facilitates monovalent ion exchange into sweat. These mechanistic components can be pharmaceutical targets to defend against hyperthermia and alleviate defective thermoregulation in the elderly2, and may provide a model relevant to more complex secretory processes.
2012-01-11 | GSE32347 | GEO
Project description:Evaporation of sweat on the skin surface is the major mechanism for dissipating heat in humans. The secretory capacity of sweat glands (SWGs) declines during aging, leading to heat intolerance in the elderly, but the mechanisms responsible for this decline remain incompletely understood. We investigated the molecular changes accompanying SWG aging in mice, where sweat tests confirmed a significant reduction of active SWGs in old mice relative to young mice. We first identified SWG-enriched mRNAs by comparing the transcriptome of Eda mutant Tabby mice, which lack SWGs, with that of wild-type control mice by RNA-sequencing analysis. This comparison revealed 171 mRNAs enriched in SWGs, including 47 mRNAs encoding core secretory proteins such as transcription factors, ion channels, ion transporters, and trans-synaptic signaling proteins. Among these, 28 SWG-enriched mRNAs showed significantly altered abundance in the aged footpad skin, and 11 of them, including Foxa1, Best2, Chrm3, and Foxc1 mRNAs belonged to the ‘core secretory’ category. Consistent with the changes in mRNA expression, immunohistology revealed that higher numbers of secretory cells from old SWGs express FOXC1 protein, the product of Foxc1 mRNA. In sum, our study identified mRNAs enriched in SWGs, including those that encode core secretory proteins, and changes in these mRNAs and proteins with SWG aging in mice.
2024-05-17 | GSE249782 | GEO
Project description:Evaporation of sweat on the skin surface is the major mechanism for dissipating heat in humans. The secretory capacity of sweat glands (SWGs) declines during aging, leading to heat intolerance in the elderly, but the mechanisms responsible for this decline remain incompletely understood. We investigated the molecular changes accompanying SWG aging in mice, where sweat tests confirmed a significant reduction of active SWGs in old mice relative to young mice. We first identified SWG-enriched mRNAs by comparing the transcriptome of Eda mutant Tabby mice, which lack SWGs, with that of wild-type control mice by RNA-sequencing analysis. This comparison revealed 171 mRNAs enriched in SWGs, including 47 mRNAs encoding core secretory proteins such as transcription factors, ion channels, ion transporters, and trans-synaptic signaling proteins. Among these, 28 SWG-enriched mRNAs showed significantly altered abundance in the aged footpad skin, and 11 of them, including Foxa1, Best2, Chrm3, and Foxc1 mRNAs belonged to the ‘core secretory’ category. Consistent with the changes in mRNA expression, immunohistology revealed that higher numbers of secretory cells from old SWGs express FOXC1 protein, the product of Foxc1 mRNA. In sum, our study identified mRNAs enriched in SWGs, including those that encode core secretory proteins, and changes in these mRNAs and proteins with SWG aging in mice.
2024-05-17 | GSE249783 | GEO
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.
| S-EPMC8784167 | biostudies-literature
Project description:To understand the mechanisms through which JunB regulates Tregs-mediated immune regulation, we examined the global gene expression profiles in the JunB WT and KO Tregs by performing RNA sequencing (RNA-seq) analysis.
2019-05-07 | GSE129060 | GEO
Project description:Background and Aims: The forkhead box A (FOXA) family of pioneer transcription factors is critical for the development of many endoderm-derived tissues including the lung and the liver. Here we investigate the role of FOXA2 in regulating intestinal epithelial cell function. Methods: ChIP-seq was used to identify FOXA2 binding sites genome-wide. Targets of FOXA2 were validated using ChIP-qPCR and siRNA-mediated depletion of FOXA1/2 followed by RT-qPCR. A luciferase-based assay was used to measure intracellular cAMP after FOXA1/2 modulation.Results: Peaks of FOXA2 occupancy were frequent at loci contributing to gene ontology pathways of regulation of cell migration, cell motion, and plasma membrane function. Depletion of both FOXA1 and FOXA2 led to a significant reduction in the expression of multiple transmembrane proteins including ion transporters. One of the targets was the adenosine A2B receptor, and reduced receptor mRNA levels were associated with a functional decrease in intracellular cAMP. We also observed that 30% of FOXA2 binding sites contained a GATA motif and that FOXA1/A2 depletion reduced GATA-4, but not GATA-6 protein levels. Conclusions: These data show that FOXA2 plays a critical role in regulating intestinal epithelial cell function. FOXA2 depletion affects the expression of ion transporters and other transmembrane proteins, which form a network essential for maintaining normal ion and solute transport. Moreover, we show that the FOXA and GATA families of transcription factors may work cooperatively to regulate gene expression genome-wide. To determine the role of FOXA2 in regulating gene expression in intestinal epithelial cells, ChIP-seq was performed for FOXA2 in Caco2 (colorectal adenocarcinoma) cells.
2015-08-06 | E-GEOD-66218 | biostudies-arrayexpress
Project description:The SLICK1 mutation confers thermotolerance to cattle inheriting one or two copies of the gene. Results are unclear as to whether the mutation changes capacity of animals to undergo sweating during heat stress. Accordingly, differences in characteristics of sweat glands between slick and wildtype Holstein heifers was determined. There were no differences in the proportion of skin occupied by sweat glands but sweat glands from slick heifers had higher amounts of immunoreactive FOXA1 than wildtype heifers. FOXA1 is a transcription factor important for sweating. While results do not support the idea that the SLICK1 mutation changes the abundance of sweat glands in skin, it did affect functional properties of sweat glands, as indicated by increased abundance of immunoreactive FOXA1.
2023-04-01 | GSE200138 | GEO
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.
| S-EPMC11335981 | biostudies-literature
Project description:Sweat has a critical role in human body, including thermoregulation and maintenance of skin environment and health. Hyperhidrosis and anhidrosis are caused by abnormalities in sweat secretion resulting in severe skin conditions (pruritus and erythema). Bioactive peptide, pituitary adenylate cyclase-activating polypeptide (PACAP) was isolated and identified to activate adenylate cyclase in pituitary cells. In recent years, it was reported that PACAP increases sweat secretion via PAC1R in mice and promotes the translocation of AQP5 to the cell membrane through increasing intercellular [Ca2+] via PAC1R in NCL-SG3 cells. However, the intracellular signaling mechanisms by PACAP are poorly clarified. In this study, we used PAC1R knockout (KO) mice and wild-type (WT) mice to observe changes in AQP5 localization and gene expression in sweat gland by PACAP treatment. Immunohistochemistry revealed that PACAP promotes the translocation of AQP5 to lumen side in eccrine gland via PAC1R. Furthermore, PACAP up-regulates gene expression (Ptgs2, Kcnn2, Cacna1s) involved in sweat secretion in WT mice. Further, PACAP treatment down-regulated Chrna1 gene expression in PAC1R KO mice. These genes were found to be involved in multiple pathways related to sweating. Overall our data provide a solid basis for future research initiatives to develop new therapies to treat sweating disorders.
2023-01-23 | GSE223124 | GEO