Project description:We hypothesize that gene expression in the aging lungs of these two strains of mice are divergent thus contributing to the disparity in the phenotypes. More specifically, (1) Aging DBA/2J mice compared to aging C57BL/6 mice are known to be accelerated in their lung physiology and morphometry; (2) C57BL/6J are known to have longer natural longevity than DBA/2J mice. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between aging lungs of both strains of mice. Keywords: comparative expression profiling
Project description:We hypothesize that gene expression in the aging lungs of these two strains of mice are divergent thus contributing to the disparity in the phenotypes.re specifically, (1) Aging DBA/2J mice compared to aging C57BL/6 mice are known to be accelerated in their lung physiology andrphometry; (2) C57BL/6J are known to have longer natural longevity than DBA/2J mice. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between aging lungs of both strains of mice. Experiment Overall Design: This study utilizes microarray analysis to test these hypotheses. Three sets of lungs were harvested from both strains at each time point (C57BL/6J: 2, 18, AND 26s; DBA/2J: 2 and 18s). RNA was isolated and used for global gene expression profiling (Affymetrixuse 430 2.0 array). Statistically significant gene expression was determined as a minimum 6 counts of 9 pairwise comparisons, minimum 1.5-fold change, and p < 0.05. Further, Absolute | FC - FC SEM | >= 1.5.
Project description:Mlycd encodes malonyl-CoA decarboxylase (MCD), which is an enzyme that localizes in the cytosolic, mitochondrial, and peroxisomal compartments and catalyzes the conversion of malonyl-CoA into acetyl-CoA. Malonyl-CoA can be converted into malonylcarnitine (C3DC). Patients with an autosomal recessive defect of MCD and MCD KO mice have pronounced elevations of C3DC. Analysis of plasma C3DC levels in the BxD genetic reference population revealed increased levels in BxD strains that harbor the DBA/2J haplotype at the site of the Mlycd gene. RNA sequencing was performed on two samples of DBA/2J mouse livers and two C57BL/6J mouse livers. Decreased expression of Mlycd gene as well as intronic reads in intron 2 were observed in DBA/2J livers. Long-read sequecing of DBA/2J livers in the Mlycd region confirmed an intracisternal A-particle (IAP) retrotransposon in intron 2 of the DBA/2J Mlycd sequence. To confirm the causal nature of the variant, DBA/2J mice with and without the C57BL/6J variant of Mlycd spliced in were tested for products of MCD enzymatic activity, and the C57BL/6J variant was able to rescue the phenotype seen in the DBA/2J mice.
Project description:Regulation of the immune response to Salmonella enterica serovar Typhimurium (S. Typhimurium) infection is a complex process, influenced by the interaction between genetic and environmental factors. Different inbred strains of mice exhibit distinct levels of resistance to S. Typhimurium infection, ranging from susceptible (e.g., C57BL/6J) to resistant (e.g., DBA/2J) strains. However, the underlying molecular mechanisms contributing to the host response remain elusive. In this study, we present a comprehensive proteomics profiling of spleen tissues from C57BL/6J and DBA/2J strains with different doses of S. Typhimurium infection by tandem tag mass coupled with two-dimensional liquid chromatography-tandem mass spectrometry (TMT-LC/LC-MS/MS). We identified and quantified 3,986 proteins, resulting in 475 differentially expressed proteins (DEPs) between C57BL/6J and DBA/2J strains. Functional enrichment analysis unveiled that the mechanism of innate immune responses to S. Typhimurium infection could be associated with several signaling pathways, including the interferon signaling pathway. We experimentally validated the roles of interferon signaling pathway in innate immune response to S. Typhimurium infection using IFN-γ neutralization assay. We further illustrated the roles of macrophage cells and pro-inflammatory cytokines in the mechanisms underlying the resistance to S. Typhimurium using qRT-PCR. Taken together, our results provide new insights into the genetic regulation of the immune response to S. Typhimurium infection in mice and might provide potential protein targets for controlling the infection.
Project description:Adolescent sensitivity to alcohol is predictive of later alcohol use and is influenced by genetic background. Data from our laboratory suggested that adolescent C57BL/6J and DBA/2J inbred mice differed in susceptibility to dorsal hippocampus-dependent contextual fear learning deficits after acute alcohol exposure. To investigate the biological underpinnings of this strain difference, we examined dorsal hippocampus gene expression via RNA-sequencing after alcohol and/or fear conditioning across male and female C57BL/6J and DBA/2J adolescents. Strains exhibited dramatic differences in dorsal hippocampal gene expression. Specifically, C57BL/6J and DBA/2J strains differed in 3526 transcripts in males and 2675 transcripts in females. We identified pathways likely to be involved in mediating alcohol’s effects on learning, including networks associated with Chrna7 and Fmr1. These findings provide insight into the mechanisms underlying strain differences in alcohol’s effects on learning and suggest that different biological networks are recruited for learning based on genetics, sex, and alcohol exposure.