Project description:Cdca7l acts as a male-specific oncogene in astrocytoma and glioblastoma, and can transform primary astrocyte growth in soft agar. We stably overexpressed Cdca7l in mouse primary astrocytes and compared gene expression to primary astrocytes expressing empty vector control in male and female cell to identify gene expression differences between male and female cells and between Cdca7l-overexpressing and normal primary astrocytes.
Project description:Cdca7l is expressed higher in male astrocytoma/GBM than female tumors or normal cells, and knockdown of Cdca7l blocks growth of male tumor cells, but not female tumor cells. We stably depleted Cdca7l in mouse astrocytoma cells and compared gene expression to control astrocytoma cells expressing non-targeting scrambled shRNA in male and female cells and to wild type primary astrocytes to identify gene expression differences between male and female cells and between Cdca7l-depleted, scrambled shRNA control cells and wild type primary astrocytes.
Project description:We identified genes expressed in mouse liver that are regulated by Cux2, a highly female-specific liver transcription factor whose expression is regulated by sex-dependent plasma GH patterns. Using siRNA to knockdown Cux2 expression in female liver, we show that female specific genes are predominantly repressed by Cux2 knockdown. In contrast, similar numbers of male-biased genes are repressed as are induced by Cux2 knockdown. A scrambled, non-specific siRNA was used as a control. (Published in: TL Conforto et al 2012, Mol Cell Biol. 2012, 32:4611-4627. PubMed PMID: 22966202; PMCID: PMC3486175)
Project description:We identified genes expressed in mouse liver that are regulated by Cux2, a highly female-specific liver transcription factor whose expression is regulated by sex-dependent plasma GH patterns. Using adenovirus to overexpress Cux2 (Adeno-Cux2) in male liver, we show that Cux2 represses ~35% of male-biased genes and induces/de-represses ~35% of female-biased genes. Adeno-CMV was used as a control for adenoviral infection. (Published in: TL Conforto et al 2012, Mol Cell Biol. 2012, 32:4611-4627. PubMed PMID: 22966202; PMCID: PMC3486175)
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:The goal of this study is to compare the sex specific effects of the expression of p53 missense mutations on the transcriptomes of male and female primary astrocytes. Primary cortical astrocytes harboring a single floxed Trp53 allele were harvested from male and female postnatal day one pups, and transduced with mutant p53;IRES GFP followed by CRE recombinase. mRNA was collected from male and female astrocytes transduce with mouse Trp53:R172H, Trp53:Y202C, or Trp53:Y217C. This study revealed sex specific gain-of-function effects on the transcriptomes of each cell line that correlated with cancer pathways.
Project description:Sex differences in liver gene expression are dictated by sex-differences in circulating growth hormone (GH) profiles. Presently, the pituitary hormone dependence of mouse liver gene expression was investigated on a global scale to discover sex-specific early GH response genes that might contribute to sex-specific regulation of downstream GH targets and to ascertain whether intrinsic sex-differences characterize hepatic responses to plasma GH stimulation. RNA expression analysis using 41,000-feature microarrays revealed two distinct classes of sex-specific mouse liver genes: genes subject to positive regulation (class-I) and genes subject to negative regulation by pituitary hormones (class-II). Genes activated or repressed in hypophysectomized (Hypox) mouse liver within 30-90min of GH pulse treatment at a physiological dose were identified as direct targets of GH action (early response genes). Intrinsic sex-differences in the GH responsiveness of a subset of these early response genes were observed. Notably, 45 male-specific genes, including five encoding transcriptional regulators that may mediate downstream sex-specific transcriptional responses, were rapidly induced by GH (within 30min) in Hypox male but not Hypox female mouse liver. The early GH response genes were enriched in 29 male-specific targets of the transcription factor Mef2, whose activation in hepatic stellate cells is associated with liver fibrosis leading to hepatocellular carcinoma, a male-predominant disease. Thus, the rapid activation by GH pulses of certain sex-specific genes is modulated by intrinsic sex-specific factors, which may be associated with prior hormone exposure (epigenetic mechanisms) or genetic factors that are pituitary-independent, and could contribute to sex-differences in predisposition to liver cancer or other hepatic pathophysiologies.
Project description:To quantify gene expression differences in olfactory epithelium between the mouse (Mus musculus) and the Nile rat (Arvicanthis niloticus), paired-end RNA sequencing (RNA-seq) was used to profile olfactory epithelium transcriptomes of six Nile rats and six mice (C57BL/6J) (one male and one female at the age of 8, 12, and 16 weeks for each species).
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.