Project description:3 x 3 comparison of the inbred strains SM/J and NZB/BinJ. Experiment Overall Design: Simple comparison of native untreated gene expression profiles of female 8wk old SM mice (x3) by female 8wk old NZB mice (x3)
Project description:Transcriptomic analysis of gene expression of splenocytes from 16-week-old female NZB/NZW F1 (BWF1) mice, which are prone to lupus, and comparison to gene expression of splenocytes from male BWF1 and female BALB/c mice, which are not prone to lupus. Results provide insight into the differences in immunological activities that make female BWF1 mice more susceptible to lupus.
Project description:NZB/WF1 female mice spontaneously develop autoimmune lupus nephritis. Expression profiling of kidney tissue from (a) 12 week NZB/W F1 female mice defined as asymptomatic for lupus nephritis, (b) 36 and 42 week NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 and 42 week NZB/W F1 female mice that are diseased/symptomatic for lupus nephritis and treated with Sirolimus was carried out. The goal of the study was to identify genes associated with lupus nephritis and modulated by Sirolimus, an inhibitor of mTOR. In addition, lupus nephritis genes resistant to Sirolimus therapy were also identfied This series of samples comprises of kidney tissue from (a) 12 week old NZB/W F1 female mice defined as asymptomatic for lupus nephritis (N=4), (b) 36 (N=3) and 42 week (N=3) old NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 (N=3)and 42 (N=3) week old NZB/W F1 female mice that are asymptomatic for lupus nephritis on treatment with Sirolimus
Project description:NZB/WF1 female mice spontaneously develop autoimmune lupus nephritis. Expression profiling of kidney tissue from (a) 12 week NZB/W F1 female mice defined as asymptomatic for lupus nephritis, (b) 36 and 42 week NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 and 42 week NZB/W F1 female mice that are diseased/symptomatic for lupus nephritis and treated with Sirolimus was carried out. The goal of the study was to identify genes associated with lupus nephritis and modulated by Sirolimus, an inhibitor of mTOR. In addition, lupus nephritis genes resistant to Sirolimus therapy were also identfied
Project description:Background: Sm proteins are multimeric RNA-binding factors, found in all three domains of life. Eukaryotic Sm proteins, together with their associated RNAs, form small ribonucleoprotein (RNP) complexes important in multiple aspects of gene regulation. Comprehensive knowledge of the RNA components of Sm RNPs is critical for understanding their functions. Results: We developed a multi-targeting RNA-immunoprecipitation sequencing (RIP-seq) strategy to reliably identify Sm-associated RNAs from Drosophila ovaries and cultured human cells. Using this method, we discovered three major categories of Sm-associated transcripts: small nuclear (sn)RNAs, small Cajal body (sca)RNAs and mRNAs. Additional RIP-PCR analysis showed both ubiquitous and tissue-specific interactions. We provide evidence that the mRNA-Sm interactions are mediated by snRNPs, and that one of the mechanisms of interaction is via base pairing. Moreover, the Sm-associated mRNAs are mature, indicating a splicing-independent function for Sm RNPs. Conclusions: This study represents the first comprehensive analysis of eukaryotic Sm-containing RNPs, and provides a basis for additional functional analyses of Sm proteins and their associated snRNPs outside of the context of pre-mRNA splicing. Our findings expand the repertoire of eukaryotic Sm-containing RNPs and suggest new functions for snRNPs in mRNA metabolism.
Project description:Sexual dimorphism of gene expression is commonly observed in mammalian tissues, including liver. To assess sexual dimorphisms in gene expression, we profiled the transcriptome of liver tissue from 20-week old male and female mice of the C57BL/6N (B6) and C3H/HeN (C3) inbred mouse strains using RNA-seq. These two inbred mouse strains exhibit phenotypic differences in liver biology, as they are at opposite ends of the spectrum of spontaneous hepatocellular carcinoma incidence; C3 mice are highly susceptible to develop spontaneous liver tumors as a function of age, while B6 mice are extremely resistant. Overall, these datasets provide insight into the underlying gene expression patterns that should be considered when assessing sex differences in mouse liver.
Project description:Background: Sm proteins are multimeric RNA-binding factors, found in all three domains of life. Eukaryotic Sm proteins, together with their associated RNAs, form small ribonucleoprotein (RNP) complexes important in multiple aspects of gene regulation. Comprehensive knowledge of the RNA components of Sm RNPs is critical for understanding their functions. Results: We developed a multi-targeting RNA-immunoprecipitation sequencing (RIP-seq) strategy to reliably identify Sm-associated RNAs from Drosophila ovaries and cultured human cells. Using this method, we discovered three major categories of Sm-associated transcripts: small nuclear (sn)RNAs, small Cajal body (sca)RNAs and mRNAs. Additional RIP-PCR analysis showed both ubiquitous and tissue-specific interactions. We provide evidence that the mRNA-Sm interactions are mediated by snRNPs, and that one of the mechanisms of interaction is via base pairing. Moreover, the Sm-associated mRNAs are mature, indicating a splicing-independent function for Sm RNPs. Conclusions: This study represents the first comprehensive analysis of eukaryotic Sm-containing RNPs, and provides a basis for additional functional analyses of Sm proteins and their associated snRNPs outside of the context of pre-mRNA splicing. Our findings expand the repertoire of eukaryotic Sm-containing RNPs and suggest new functions for snRNPs in mRNA metabolism. RNA-Immunoprecipitation sequencing of RNA-Sm protein complexes.
Project description:PF-04287881 induced varying degrees of liver necrosis and phospholipidosis in a 34-inbred strain Mouse Diversity Panel (MDP) study. Four strains with differing susceptibilities to these phenotypes (MA/MyJ, NZW/LacJ, SM/J, WSB/EiJ) were selected for analysis of gene expression changes in the liver. The objective of this study was to identify gene expression changes that drive PF-04287881-induced liver injury.
Project description:A QTL analysis between inbred mouse strains MRL/MpJ and SM/J was performed to identify genetic loci influencing high-density lipoprotein (HDL) cholesterol and triglycerides (TG) at eight weeks of age in F2 mice fed a chow diet. In order to narrow down lists of candidate genes, expression levels from liver tissue were used to test for differential expression among parental and F1 strains and to scan for eQTL in F2 animals. We provide evidence for Mppe1 (Chr 18) as an HDL QTL candidate gene and Cyp2d26 (Chr 15) as a TG QTL candidate gene.
Project description:The purpose of this study was to examine the effect of aldosterone receptor blockade on the immunopathogenesis and progression of nephritis in the (NZBxNZW) F1 murine lupus model. Female NZB/W F1 mice (11 weeks old) were treated daily with 25 or 50 mg/kg of oral spironolactone or vehicle. Proteinuria, renal function and serum autoantibody levels were monitored. Renal histopathology, immune complex deposition, and immunohistochemistry were analyzed at various time points. Targeted microarray analysis was performed on renal tissue, with subsequent real time PCR analysis of several differentially expressed genes. Keywords: treatment study