Project description:Genetic variation is known to influence the amount of mRNA produced by a gene, but the effects in different tissues is unclear. We studied gene expression levels in whole brain, kidney or liver, comparing 8 week old, male C57BL/6J to DBA/2J mice. Genes differentially expressed due to genetic background in one tissue were not differentially expressed in other tissues, suggesting that genetic variation of gene expression is tissue specific in inbred mice. Data used in a comparison to the BXD panel of mice in GSE8355, GSE8356, GSE6621 and to SJL/J in GSE8358.
Project description:The ability to generate defined null mutations in mice revolutionized the analysis of gene function in mammals. However, gene-deficient mice generated by using 129-derived embryonic stem (ES) cells may carry large segments of 129 DNA, even when extensively backcrossed to reference strains, such as C57BL/6J, and this may confound interpretation of experiments performed in these mice. Tissue plasminogen activator (tPA), encoded by the PLAT gene, is a fibrinolytic serine protease that is widely expressed in the brain. A large number of neurological abnormalities have been reported in tPA-deficient mice. The studies here compare genes differentially expressed in the brains of Plat-/- mice from two independent Plat-/- mouse derivations to wild-type C57BL/6J mice. One strain denoted “Old” was constructed in ES cells from a 129 mouse and backcrossed extensively to C57BL/6J, and one denoted “New” Plat-/- mouse was constructed using zinc finger nucleases directly in the C57BL/6J-Plat-/- mouse strain. We identify a significant set of genes that are differentially expressed in the brains of Old Plat-/- mice that preferentially cluster in the vicinity of Plat on chromosome 8, apparently linked to more than 20 Mbp of DNA flanking Plat being of 129 origin. No such clustering is seen in the New Plat-/- mice.
Project description:TLR4 deficiency attenuates kidney injury after ischemic reperfusion as measured by both renal function and morphology. To better understand the role of TLR4 during the acute kidney injury, we used DNA microarray to identify genes that were differentially expressed on kidneys in wildtype B10 mice and TLR4 null mice during the early stage of injury. A murine ischemic reperfusion injury model was established. After right nephrectomy, the left pedicle was clamped for 23min followed by 4hr reperfusion. Sham mice were used as controls. 6 WT males and 6 TLR4 null males were included with 3 ischemic and 3 shams in each group.
Project description:We aimed to identify urinary exosomal ncRNAs as novel biomarkers for diagnosis of Chronic Kidney Disease (CKD) for this, we examined 15 exosomal ncRNA profiles in urine samples from CKD patients from four different stages (I, II, III and IV) and compared them to 10 healthy controls. We identified a significant number of novel, differentially expressed ncRNAs in CKD patients compared to healthy, which might be employed as early diagnostic markers in CKD in the future.
Project description:TLR4 deficiency attenuates kidney injury after ischemic reperfusion as measured by both renal function and morphology. To better understand the role of TLR4 during the acute kidney injury, we used DNA microarray to identify genes that were differentially expressed on kidneys in wildtype B10 mice and TLR4 null mice during the early stage of injury.
Project description:Purpose: To define differentially regulated pathways in heart tissue from mice with chornic kidney disease (CKD) compared to age-matched controls. Methods: CKD was induced in 5-week-old, male 129X1/SvJ mice (JAX) through five-sixths nephrectomy in a two-step surgery (n=5). Age-matched mice undergoing bilateral sham surgeries served as controls (n=5). Heart tissue was collected at 8 weeks of CKD for next generation sequencing. Results: Hearts from mice with uremic cardiomyopathy yielded over 1,000 differentially-expressed mRNA transcripts compared to hearts from age-matched, sham-operated mice. Ingenuity biofunctions analysis identified significant enrichment for genes involved in Tissue Morphology, Immune Cell Trafficking, Cardiovascular Development and Function, and Humoral Immune Response. We focused on Ingenuity canonical pathways involving inflammation and immune system function including pathways needed for a T-cell mediated response: leukocyte extravasation, antigen presentation, dendritic cell maturation, T cell co-stimulatory signaling, and T-helper cell differentiation. Conclusions: Left ventricles from mice with CKD display differential expression in a number of pathways suggesting inflammation and surprisingly involved genes involved in the adaptive immune system.
Project description:Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that factors on chromosomes (chr) 8, 11, and 18 are responsible for susceptibility to S. aureus sepsis in A/J mice. F1 mice from C57BL/6J X CSS8 cross (C8A) and C57BL/6J X CSS18 (C18A) were also susceptible to S. aureus (median survival < 48 h), whereas F1 mice from C57BL/6J X CSS11 cross (C11A) were resistant (median survival > 120 h) to S. aureus. Bacterial loads in the kidney were consistent with F1 median survivals, with higher bacterial counts in susceptible mice. No sexlinked associations with susceptibility were noted in F1 intercrosses. Using whole genome transcription profiling, we identified a total of 192 genes on chromosomes 8, 11, and 18 which are differentially expressed between A/J and C57BL/6J in the setting of S. aureus infection. Of these, 28 genes had Gene Ontology annotations indicating a potential immune response function. These 28 genes are associated with susceptibility to S. aureus in A/J mice, and are potential determinants of susceptibility to S. aureus infection in humans.
Project description:Eight weeks after C57BL / 6J mice fed a high-fat diet (HFD), the degree of insulin resistance was assessed by intraperitoneal glucose tolerance test (IPGTT) and the insulin resistance model was successfully established. Mice were then treated with resveratrol and metformin for 6 weeks and blood and liver tissue samples were collected. Blood biochemical parameters were determined by kit, protein expression of hepatic insulin signaling pathway mRNA and mRNA was determined by Western blot and real-time polymerase chain reaction, and histomorphological changes were observed by histological staining. Mouse liver tissue samples were detected by high-throughput sequencing technology to obtain differential lncRNA expression profiles. Further differentially expressed genes were analyzed using bioinformatics techniques.