Project description:The absence of the Rb tumor suppressor gene changes levels/activities of transcription factors (e.g., E2F and p53) which alter gene expression patterns, related to cell cycle control and cellular response to DNA damage. Cisplatin is a genotoxic chemotherapeutic agent and wildtype or Rb null cells have different sensitivities to cisplatin-induced cytotoxicity. We used microarrays to compare global profiles of gene expression and distinct responses of wildtype and Rb null MEFs in response to cisplatin. Experiment Overall Design: Primary wildtype or Rb null MEFs were generated from embryos at embryonic day 13.5 and cultured to passage 2. Wildtype or Rb null MEFs were either untreated or treated with 16 microM cisplatin for 24 hours prior to harvest and RNA extraction. Four different RNA samples (wildtype or Rb-/- MEFs, untreated or cisplatin-treated) were used for hybridization in triplate to Affimatrix Chips. Then, the total of 12 hybridizations were divided into 4 subseries: UT-Rb, UT-WT, CP-Rb, CP-Wt, and each subseries contained three samples (hybridization 1-3 or a-c).
Project description:The absence of the Rb tumor suppressor gene changes levels/activities of transcription factors (e.g., E2F and p53) which alter gene expression patterns, related to cell cycle control and cellular response to DNA damage. Cisplatin is a genotoxic chemotherapeutic agent and wildtype or Rb null cells have different sensitivities to cisplatin-induced cytotoxicity. We used microarrays to compare global profiles of gene expression and distinct responses of wildtype and Rb null MEFs in response to cisplatin. Keywords: genotype and cisplatin treatment
Project description:The RB and p53 tumor suppressor pathways regulate the transcription of genes involved in cell cycle progression, DNA replication, DNA repair, and apoptosis. These tumor suppressors are critical modulators of the response to genotoxic damage and both pathways are frequently inactivated in human cancers. We used microarrays to monitor gene expression patterns upon exposure to cisplatin treatment in fibroblasts harboring loss/inactivation of RB and/or p53. We generated mouse adult fibroblasts harboring loss/inactivation of RB and/or p53 and subjected these cell populations to cisplatin treatment for 24 hours. Treated cell populations were allowed to recover from cisplatin exposure, generating a recurred cell popuation. Untreated and recurred cell populations were then subjected to RNA extraction and hybridization on Affymetrix microarrays.
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: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.