Project description:In mammals, expansion of adipose tissue mass induces accumulation of adipose tissue macrophages (ATMs). We isolated CD11c- (FB) and CD11c+ (FBC) perigonadal ATMs from SVCs of lean (C57BL/6J Lep +/+) and obese leptin-deficient (C57BL/6J Lep ob/ob) mice. We used expression microarrays to generate transcription profiles of perigonadal ATMs from lean (C57BL/6J Lep +/+) and obese (C57BL/6J Lep ob/ob) mice. Profiling purified FBs and FBCs, we identified 521 transcripts whose expression was differentially (nominal p-value < 0.01) expressed between FBs from lean and obese mice and 1509 genes whose expression was differentially (nominal p-value <0.01) expressed between FBC from lean and obese mice
Project description:Analysis of angiotensin II effect on left ventricle at gene expression level. The hypothesis tested in the present study was that angiotensin II treatment may affect gene expression in left ventricle in a strain specific manner. Results provide important information about which genes respond to angiotensin II in C57Bl/6N male mice compared to their C57Bl/6J counterparts. Total RNA obtained from isolated left ventricles from C57Bl/6J and C57Bl/6N mice subjected to 48 hours of angiotensin II infusion, via osmotic mini-pumps (500ng/kg/h) implanted sub-cutaneously, compared to sham operated controls.
Project description:Rationale: Chagasic disease is associated with high morbidity in Latin America. Acute Chagasic myocarditis is consistently found in acute infections but little is known about its contribution to chronic cardiomyopathy. The aim of the study was to phenotypically characterize two strains of mice with differential Chagas infection susceptibility and correlate strain myocarditis phenotypes with heart tissue gene expression. Methods: C57BL/6J and Balb/c mice were injected intraperitoneally with 0 or 150-200 tissue-derived trypomastigotes (Tulahuen strain). Echocardiograms, brain natriuretic peptide and troponin were measured. Heart tissue was harvested for histopathological analysis and gene expression profiling on microarrays. Genes differently expressed between infected Balb/c and C57BL/6J were identified Results: Echocardiograms demonstrated differences in heart rate in Balb/c vs. C57BL/6J infected mice: 413 vs. 476 bpm, (p=0.0001), stroke volume: 31.9 ± 9.3 vs. 39.2 ± 5.5 µl (p=0.03); and cardiac output: 13.1 ± 3.5 vs. 18.7 ± 3.2 µl/min (p=0.002). Gene expression at 4 weeks analysis demonstrated 32 statistically significant (q-value < 0.05) differentially expressed genes between infected Balb/c and C57BL/6J which were enriched for genes related to protein kinase B (AKT) pathway 8 Balb/c mice and 8 C57BL/6J mice were infected and 8 Balb/c and 8 C57BL/6J were used as controls. 6 mice per group were used for gene expression analysis.
Project description:Rationale: Chagasic disease is associated with high morbidity in Latin America. Acute Chagasic myocarditis is consistently found in acute infections but little is known about its contribution to chronic cardiomyopathy. The aim of the study was to phenotypically characterize two strains of mice with differential Chagas infection susceptibility and correlate strain myocarditis phenotypes with heart tissue gene expression. Methods: C57BL/6J and Balb/c mice were injected intraperitoneally with 0 or 150-200 tissue-derived trypomastigotes (Tulahuen strain). Echocardiograms, brain natriuretic peptide and troponin were measured. Heart tissue was harvested for histopathological analysis and gene expression profiling on microarrays. Genes differently expressed between infected Balb/c and C57BL/6J were identified Results: Echocardiograms demonstrated differences in heart rate in Balb/c vs. C57BL/6J infected mice: 413 vs. 476 bpm, (p=0.0001), stroke volume: 31.9 ± 9.3 vs. 39.2 ± 5.5 µl (p=0.03); and cardiac output: 13.1 ± 3.5 vs. 18.7 ± 3.2 µl/min (p=0.002). Gene expression at 4 weeks analysis demonstrated 32 statistically significant (q-value < 0.05) differentially expressed genes between infected Balb/c and C57BL/6J which were enriched for genes related to protein kinase B (AKT) pathway
Project description:Analysis of angiotensin II effect on left ventricle at gene expression level. The hypothesis tested in the present study was that angiotensin II treatment may affect gene expression in left ventricle in a strain specific manner. Results provide important information about which genes respond to angiotensin II in C57Bl/6N male mice compared to their C57Bl/6J counterparts.
Project description:This study used Illumina strand-specific, paired-end RNA-sequencing to examine gene expression differences between normal and neoplastic mouse pancreatic ductal cells grown as three-dimensional, organoid cultures. The study analyzed 19 independently derived organoid lines. These 19 lines included 7 biological replicate "mN," or mouse normal, organoid lines, derived from the pancreatic ductal cells of wild-type C57Bl/6J or C57Bl/6N mice. In addition, the study analyzed 6 biological replicate "mP," or mouse PanIN, organoid lines, derived from PanIN-containing mouse pancreata from the KrasLSL-G12D; Pdx1-Cre mouse model. (The presence of PanIN in the pancreata from which these organoid lines were derived was confirmed by examining histological sections from the same pancreata). The final 6 lines examined in this study were biological replicate "mT," or mouse tumor, organoid lines, derived from mouse pancreata containing pancreatic ductal adenocarcinoma (PDAC) from the KrasLSL-G12D; Trp53LSL-R162H; Pdx1-Cre mouse model. We genes differentially expressed in the PanIN- or tumor-derived mouse organoid lines, relative to the mouse normal organoids, that may reflect expression changes required for pancreatic tumorigenesis.
Project description:RNA-seq analysis were applied to elucidate the transcriptional differences of wild-type and Abcb11-deficient mice. Comparison of female Abcb11-/- (Abcb11F) and female C57BL/6J mouse (WTF) livers identified 3,652 RNA species that were differentially expressed (1,809 genes upregulated and 1,843 genes downregulated; Padj < 0.05). Comparison of liver gene expression in Abcb11F versus non-tumor tissue of female Abcb11-/- mice (NTF) revealed 47 differentially expressed genes. Cross-comparison of the lists of differentially expressed genes in Abcb11F versus WTF and in Abcb11F versus NTF revealed 36 genes common to the two data sets.
Project description:Although mitochondrial dysfunctions are implicated in the pathogenesis of obesity, the molecular mechanisms underlying obesity-related metabolic abnormalities are still not well established. To acquire a comprehensive picture of mitochondrial molecular changes within metabolically active tissues, we focused on hepatic and muscle whole cellular transcriptome and mitochondrial proteome alterations in 16 and 48 weeks old high fat diet (HFD)-feed wild type C57BL/6J and hyperphagic, genetically modified mice with leptin dysfunction (ob/ob and db/db). On transcriptome level, the most discriminative hepatic alterations distinguished between genetically modified and wild type mice, and between overnight fasted and non-fasted mice, while the muscle transcriptional alterations related mainly to the fasting state. The fractions of uniquely different proteins were consistently higher in hyperphagic than in HFD-fed mice and in fasted than non-fasted mice . The liver samples revealed overall higher number of differentially expressed RNAs and proteins than muscle samples. Differentially expressed genes and proteins in the liver, but not in the muscle, could be assigned to several Gene Ontology terms, including oxidation-reduction and several metabolic processes. Thus, altered expression of genes and proteins accompanied the state of obesity and was quantitatively different in the liver and muscle. Our parallel microarray- and quantitative mitochondrial mass spectrometry-based study performed on hepatic and muscle samples identified a higher number of differentially expressed proteins than any other studies investigating obesity-related proteomes. However, even with our integrated transcriptomic and proteomic approach still many details and dynamics of a chain of metabolic events leading to obesity-related mitochondrial dysfunctions remain unresolved . 48 samples each of liver and muscle (total samples: 96). Samples splitted equally according to 3 criterions: age (24 young/24 old), fasting status (24 fasted/24 non fasted), and strain+diet (12 each: B6.V-Lep ob/J+D12450B, B6.BKS(D)-Lep rdb/J+D12450B, C57BL/6J+D12450B, C57BL/6J+D12492). Overall 3 replicates for each strain+diet/age/fasting_status combination. Low fat diet = D12450B; high fat diet = D12492.
Project description:In mammals, expansion of adipose tissue mass induces accumulation of adipose tissue macrophages (ATMs). We isolated CD11c- (FB) and CD11c+ (FBC) perigonadal ATMs from SVCs of lean (C57BL/6J Lep +/+) and obese leptin-deficient (C57BL/6J Lep ob/ob) mice. We used expression microarrays to generate transcription profiles of perigonadal ATMs from lean (C57BL/6J Lep +/+) and obese (C57BL/6J Lep ob/ob) mice. Profiling purified FBs and FBCs, we identified 521 transcripts whose expression was differentially (nominal p-value < 0.01) expressed between FBs from lean and obese mice and 1509 genes whose expression was differentially (nominal p-value <0.01) expressed between FBC from lean and obese mice RNA was isolated from sorted FBC (F4/80+, CD11b+, CD11c+) cells and FB ( F4/80+, CD11b+, CD11c-) cells and using RNeasy micro-kits (Qiagen), using a PicoPure RNA isolation kit then amplified two-rounds. Labeled cRNA Mouse Genome 430 2.0 arrays (purified FB and FBC adipose tissue macrophages. There was a total of sixteen samples. FB and FBC populations were isolated from 4 lean and 4 obese mice.
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. To identify genes for which differential expression between A/J and C57BL/6J mice could contribute to host susceptibility to S. aureus infection, we compared the gene expression profiles between uninfected A/J and C57BL/6J mice and between infected A/J and C57BL/6J mice at 2, 4, 6, and 12 hours after infection.