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Gene expression comparison of liver tissue from C57BL/6J and KK/HIJ mice

ABSTRACT: A QTL intercross was performed bewteen C57BL/6J and KK/HIL for albuminurea, asthma and cardiovascular related phenotypes. Several QTL were identified for most phenotypes. We performed microarray analysis from liver samples to identify genes differentially expressed between the parental strains. The results helped us narrow down the QTL and identify the candidate genes based on differential expression between the parental strains.

ORGANISM(S): Mus musculus

PROVIDER: GSE37429 | GEO | 2012/10/18

SECONDARY ACCESSION(S): PRJNA160125

REPOSITORIES: GEO

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Gene expression comparison of liver tissue from C57BL/6J and KK/HIJ mice

Project description:A QTL intercross was performed bewteen C57BL/6J and KK/HIL for albuminurea, asthma and cardiovascular related phenotypes. Several QTL were identified for most phenotypes. We performed microarray analysis from liver samples to identify genes differentially expressed between the parental strains. The results helped us narrow down the QTL and identify the candidate genes based on differential expression between the parental strains. At 8 weeks of age, the large lobe of the liver from 3 male and 3 females C57BL/6J and KK/HIJ (12 mice total) was collected. The mice were separated individuallly for 3 days and fasted for 4 hours prior to the tissue collection. The mice were sacrificed by cervically dislocation and perfused with PBS prior to the liver collection.

2012-10-18 | E-GEOD-37429 | biostudies-arrayexpress

Phosphoproteomics of Pseudomonass aeruginosa with KK and KKP overproduction

Project description:To determined the effects of KK and KKP on the phosphorylation levels of proteins in PAO1, we overexpressed KK and KKP separately in PAO1 cells via pHERD20T based plasmids.

2024-07-20 | PXD035228 | Pride

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KK-LC-1 as a feasible therapeutic target to eliminate ALDH+ stem cells in triple negative breast cancer

Project description:Failure to achieve complete elimination of triple negative breast cancer (TNBC) stem cells after adjuvant therapy is associated with poor outcomes. Aldehyde dehydrogenase 1 (ALDH1) is a marker of breast cancer stem cells (BCSCs), and its enzymatic activity regulates tumor stemness. Identifying upstream targets to control ALDH+ cells may facilitate TNBC tumor suppression. Here, we show that KK-LC-1 determines the stemness of TNBC ALDH+ cells via binding with FAT1 and subsequently promoting its ubiquitination and degradation. This compromised the Hippo pathway and led to nuclear translocation of YAP1 and ALDH1A1 transcription. These findings identified the KK-LC-1-FAT1-Hippo-ALDH1A1 pathway in TNBC ALDH+ cells as a therapeutic target. To reverse the malignancy due to KK-LC-1 expression, we employed a novel computational approach and discovered Z839878730 (Z8) as an small-molecule inhibitor which may disrupt KK-LC-1 and FAT1 binding. We demonstrate that Z8 suppressed TNBC tumor growth via a mechanism that reactivated the Hippo pathway and decreased TNBC ALDH+ cell stemness and viability.

2023-04-12 | PXD040200 | Pride

Gene expression profiles of KK.Cg-Ay/J (KKAy) mice and KK-a/a (KKa) mice

Project description:The differential gene expression in hepatocytes was compared between the KK.Cg-Ay/J mice and the KK-a/a mice, corresponding to the Diabetic strain and the control. The microarrays were used to screen the candidates supporting to the essential pathogenesis of Type-2 Diabetes in the pre-developing, early and developing stages, corresponding to the 6 weeks, 16 weeks and 42 weeks. To determine the significant biological processes and pathways contributing to development of Diabetic phenotypes in the KKAy mouse, we identified the candidates with the differential gene expression of the livers by comparison of the KKAy and KKa mice. These genes have relationship linkage to construct the networks for mechanistic explanation of the disease.

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Project description:The differential DNA methylation in hepatocytes was compared between the KK.Cg-Ay/J mice and the KK-a/a mice, corresponding to the Diabetic strain and the wild-type known as control. The methylation microarrays were used to support gene expression for screening the candidates susceptibility to the pathogenesis of Type-2 Diabetes in the pre-development, early and development stages, corresponding to the 6, 16 and 42 weeks old. To determine the methylation-dependent biological processes and pathways contributing to development of Diabetic phenotypes in the KKAy mouse, we identified the candidates with the differential DNA methylation levels between the KKAy and KKa mice. The expression of methylation-dependent genes have relationship linkage to construct the networks for mechanistic explanation of the disease.

2018-12-13 | GSE120865 | GEO

Genetic Loci that Regulate Ectopic Calcification in Response to Knee Trauma in LG/J by SM/J Advanced Intercross Mice

Project description:Ectopic calcification in synovial tissues is devastating to diarthrodial joints. While some forms of synovial ectopic calcification have genetically simple basis, most cases manifest as complex traits with environmental and multigenic components. The location of causal loci or the physiological processes affected by allelic variants is poorly understood. Here, we report on genetic susceptibility to ectopic calcification in the LG/J and SM/J advanced intercross mice. Using 347 mice in 98 full-sibships, destabilization of medial meniscus was performed to induce joint injury. We performed quantitative trait locus (QTL) analysis to map calcification phenotypes to discrete genomic locations. To validate the functional significance of the selected QTL candidate genes, we compared mRNA expression between parental LG/J and SM/J inbred strains. Our findings showed that joint destabilization instigated ectopic calcifications as detected and quantified by micro-CT. Overall, we detected 20 QTLs affecting synovial and meniscus calcification phenotypes with 11 QTLs linked to synovial calcification. Functional and bioinformatic analyses of single nucleotide polymorphism identified functional classifications relevant to angiogenesis (Myo1e, Kif26b, Nprl3, Stab2, Fam105b), bone metabolism/calcification (Tle3, Tgfb2, Lipc, Nfe2l1, Ank, Fam105b), arthritis (Stab2, Tbx21, Map4k4, Hoxb9, Larp6, Col1a2, Adam10, Timp3, Nfe2l1, Trpm3), and ankylosing-spondylitis (Ank, Pon1, Il1r2, Tbkbp1) indicating that ectopic calcification involves multiple mechanisms. Furthermore, the expression of 11 candidate genes was significantly different between LG/J and SM/J. Correlation analysis showed that Aff3, Fam81a, Syn3, and Ank were correlated with synovial calcification. Our findings of multiple genetic loci affecting the phenotype suggest the involvement of multiple genes contributing to its pathogenesis.

2015-01-09 | GSE64793 | GEO

Hepatic gene expression profiles in persimmon peel extract administrated KK-Ay mice

Project description:We have shown in a previous study that the intake of persimmon peel (PP) extract altered hepatic gene expression of insulin signaling and enhanced tyrosine phosphorylation of insulin receptors in nonobese type 2 diabetic Goto–Kakizaki rats. We also showed the alteration of gene expression in fatty acid synthesis and metabolism. To evaluate the effect of PP extract on obese diabetic KK-Ay mice, we fed them a diet mixed with 0.1% of the extract for 8 weeks. The plasma total ketone bodies level of the treated mice were significantly lower than that of the untreated mice. The hepatic gene expression profiles of treated mice indicated upregulation of fatty acid biosynthesis-associated gene expression. Hepatic nonesterified palmitic acid content was higher in treated mice than in untreated mice. These results suggest that the intake of PP extract enhances hepatic fatty acid biosynthesis of KK-Ay mice, reducing their plasma total ketone bodies level.

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Gene expression in soleus muscle of mouse inbred strains LG/J and SM/J

Project description:Variability in muscle mass significantly impacts energy expenditure, influencing preponderance to obesity and recently it has been reported that there is a positive association between muscle mass and longevity in older adults. Muscle fibre cross-sectional area (CSA) and proportion of different fibre types are important determinants of muscle mass, function and overall metabolism. Genetic variation plays a substantial role in phenotypic variation of these traits but the underlying genes remain poorly understood. We identified QTL associated with these muscle fibre phenotypes and hypothesized that if the phenotypic effect of the QTL was brought about by the allele specific abundance of transcripts encoded by genes within the QTL, such genes would be differentially expressed in the transcriptome between the parental strains. In this experiment, the expressed transcriptome in soleus muscle of mouse LG/J and SM/J strains was examined by measurement of gene expression on microarrays to facilitate nomination of candidate genes within identified QTL. Hypothesis driven analysis of differential expression in soleus muscle was performed between LG/J and SM/J strains for the genes in the most robust QTLs affecting fibre CSA or % Type I fibres.

2017-01-23 | E-MTAB-5290 | biostudies-arrayexpress

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