Project description:Pancreatic islets adapt to insulin resistance of pregnancy by up regulating beta-cell proliferation and increase insulin secretion. Previously, we found that prolactin receptor (Prlr) signaling is important for this process, as heterozygous prolactin receptor-null (Prlr+/-) mice are glucose intolerant, had a lower number of beta cells and lower serum insulin levels than wild type mice during pregnancy. However, since Prlr expression is ubiquitous, to determine its beta-cell-specific effects, we generated a transgenic mouse with a floxed Prlr allele under the control of an inducible promoter, i.e. bPrlR-/- mice, allowing conditional deletion of Prlr from beta cells in adult mice. In this study, we found that beta-cell-specific Prlr reduction resulted in elevated blood glucose during pregnancy. Similar to our previous finding in mice with global Prlr reduction, beta-cell-specific Prlr loss led to a lower beta-cell mass and a lower in vivo insulin level during pregnancy. However, these islets do not have an intrinsic insulin secretion defect when tested in vitro. Interestingly, when we compared the islet gene expression profile, using islets isolated from mice with global versus beta-cell-specific Prlr reduction, we found differences in expression of genes that regulate apoptosis, synaptic vesicle function and neuronal development. Indeed, islets from pregnant Prlr+/- mice are more susceptible glucolipotoxicity than bPrlR+/- islets. These observations suggest that Prlr has both cell-autonomous and non-cell-autonomous effect on beta cells, beyond its regulation of pro-proliferative genes.
Project description:ABSTRACT:Pregnancy requires a higher functional beta cell mass and this is associated with profound changes in the gene expression profile of pancreatic islets. Taking Tph1 as a sensitive marker for pregnancy-related islet mRNA expression in female mice, we previously identified prolactin receptors and placental lactogen as key signalling molecules. Since beta cells from male mice also express prolactin receptors, the question arose whether male and female islets have the same phenotypic resilience at the mRNA level during pregnancy. We addressed this question in vitro, by using islet tissue culture with placental lactogen and in vivo, by transplanting male or female islets into female acceptor mice. Additionally, the islet mRNA expression of pregnant prolactin receptor deficient mice was compared with that of their pregnant wild-type littermates. When cultured with placental lactogen, or transplanted in female recipients that became pregnant (day 12.5), male islets induced the ‘islet pregnancy gene signature’, which we defined as the 12 highest induced genes in non-transplanted female islets at day 12.5 of pregnancy. In addition, serotonin immunoreactivity was also induced in these male transplanted islets at day 12.5 of pregnancy. In order to investigate the importance of prolactin receptors in these mRNA changes we used a prolactin receptor deficient mouse model. For the 12 genes of the signature, which are highly induced in control pregnant mice, no significant induction of mRNA transcripts was found at day 9.5 of pregnancy. Together, our results support the key role of placental lactogen as a circulating factor that can trigger the pregnancy mRNA profile in male and female beta cells. Islets were isolated from non-prengant (NP) and pregnant (day 9.5) PRLR+/+ and PRLR-/- mice for RNA extraction and hybridization on Affymetrix microarrays. For every condition 3 biological replicates were 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: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.
Project description:ABSTRACT:Pregnancy requires a higher functional beta cell mass and this is associated with profound changes in the gene expression profile of pancreatic islets. Taking Tph1 as a sensitive marker for pregnancy-related islet mRNA expression in female mice, we previously identified prolactin receptors and placental lactogen as key signalling molecules. Since beta cells from male mice also express prolactin receptors, the question arose whether male and female islets have the same phenotypic resilience at the mRNA level during pregnancy. We addressed this question in vitro, by using islet tissue culture with placental lactogen and in vivo, by transplanting male or female islets into female acceptor mice. Additionally, the islet mRNA expression of pregnant prolactin receptor deficient mice was compared with that of their pregnant wild-type littermates. When cultured with placental lactogen, or transplanted in female recipients that became pregnant (day 12.5), male islets induced the ‘islet pregnancy gene signature’, which we defined as the 12 highest induced genes in non-transplanted female islets at day 12.5 of pregnancy. In addition, serotonin immunoreactivity was also induced in these male transplanted islets at day 12.5 of pregnancy. In order to investigate the importance of prolactin receptors in these mRNA changes we used a prolactin receptor deficient mouse model. For the 12 genes of the signature, which are highly induced in control pregnant mice, no significant induction of mRNA transcripts was found at day 9.5 of pregnancy. Together, our results support the key role of placental lactogen as a circulating factor that can trigger the pregnancy mRNA profile in male and female beta cells. The data obtained from the normal islets of pregnant mice (day12.5) was already described in Schraenen et al. 2010 (PMID: 20886204 and PMID: 20938637). Islets and islet grafts were isolated from non-prengant and pregnant mice for RNA extraction and hybridization on Affymetrix microarrays. For every condition, at least 3 biological replicates were used.
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.