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Microarray analysis of defective cartilage in Hoxc8- and Hoxd4-transgenic mice

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE19002 | GEO | 2010/10/15

SECONDARY ACCESSION(S): PRJNA120435

REPOSITORIES: GEO

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Microarray Analysis of Defective Cartilage in Hoxc8- and Hoxd4-Transgenic Mice.

Project description:ObjectiveHomeobox genes of the Hox class are required for proper patterning of skeletal elements and play a role in cartilage differentiation. In transgenic mice with overexpression of Hoxc8 and Hoxd4 during cartilage development, the authors observed severe defects, namely, physical instability of cartilage, accumulation of immature chondrocytes, and decreased maturation to hypertrophy. To define the molecular basis underlying these defects, the authors performed gene expression profiling using the Affymetrix microarray platform.ResultsPrimary chondrocytes were isolated from Hoxc8- and Hoxd4-transgenic mouse embryo rib cartilage at 18.5 days of gestation. In both cases, differentially expressed genes were identified that have a role in cell proliferation and cell cycle regulation. A comparison between the controls for both experimental groups did not reveal significant differences, as expected. However, the repertoires of differentially expressed genes were found not to overlap between Hoxc8- and Hoxd4-transgenic cartilage. This included different Wnt genes, cell cycle, and apoptosis regulators.ConclusionOverexpression of Hoxc8 and Hoxd4 transcription factors alters transcriptional profiles in chondrocytes at E18.5. The differences in repertoires of altered gene expression between the 2 transgenic conditions suggest that the molecular mechanisms underlying the cartilage defects may be different in both transgenic paradigms, despite apparently similar phenotypes.

| S-EPMC4297070 | biostudies-literature

Microarray analysis of defective cartilage in Hoxc8- and Hoxd4-transgenic mice

Project description:This SuperSeries is composed of the following subset Series: GSE18991: Overexpression of Hoxd4 transcription factor alters transcriptional profiles in mouse chondrocytes at E18.5 GSE18992: Overexpression of Hoxc8 transcription factor alters transcriptional profiles in mouse chondrocytes at E18.5!Series_overall_design = Refer to individual Series Refer to individual Series

2010-10-15 | E-GEOD-19002 | biostudies-arrayexpress

Microarray analysis of defective cartilage in Hoxc8- and Hoxd4-transgenic mice

Project description:Microarray analysis of defective cartilage in Hoxc8- and Hoxd4-transgenic mice

| PRJNA120435 | ENA

Expression of cartilage developmental genes in Hoxc8- and Hoxd4-transgenic mice.

Project description:Hox genes encode transcription factors, which regulate skeletal patterning and chondrocyte differentiation during the development of cartilage, the precursor to mature bone. Overexpression of the homeobox transcription factors Hoxc8 and Hoxd4 causes severe cartilage defects due to delay in cartilage maturation. Matrix metalloproteinases (MMPs), bone morphogenetic proteins (BMPs) and fibroblastic growth factors (FGFs) are known to play important roles in skeletal development and endochondral bone formation and remodeling. In order to investigate whether these molecules are aberrantly expressed in Hoxc8- and/or Hoxd4-transgenic cartilage, we performed quantitative RT-PCR on chondrocytes from Hox-transgenic mice. Gene expression levels of Bmp4, Fgf8, Fgf10, Mmp9, Mmp13, Nos3, Timp3, Wnt3a and Wnt5a were altered in Hoxc8-transgenic chondrocytes, and Fgfr3, Ihh, Mmp8, and Wnt3a expression levels were altered in Hoxd4-transgenic chondrocytes, respectively. Notably, Wnt3a expression was elevated in Hoxc8- and reduced in Hoxd4-transgenic cartilage. These results suggest that both transcription factors affect cartilage maturation through different molecular mechanisms, and provide the basis for future studies into the role of these genes and possible interactions in pathogenesis of cartilage defects in Hoxc8- and Hoxd4-transgenic mice.

| S-EPMC2814844 | biostudies-literature

Expression of folate pathway genes in the cartilage of Hoxd4 and Hoxc8 transgenic mice.

Project description:BACKGROUND:Hox transcription factors are well known for their role in skeletal patterning in vertebrates. They regulate gene expression during the development of cartilage, the precursor to mature bone. We previously reported that overexpression of the homeobox genes Hoxc8 and Hoxd4 results in severe cartilage defects, reduced proteoglycan content, accumulation of immature chondrocytes, and decreased maturation to hypertrophy. We have also shown that Hoxd4 transgenic mice whose diets were supplemented with folate had their skeletal development restored. Since folate is required for growth and differentiation of chondrocytes, we hypothesized that the beneficial effect of folate in Hoxd4 transgenic mice might indicate a local deficiency in folate utilization, possibly caused by deregulation of genes encoding folate transport proteins or folate metabolic enzymes. METHODS:We assayed the prevalence of transcripts for 22 folate transport proteins and metabolizing enzymes, here collectively referred to as folate pathway genes. Quantitative real-time PCR was performed on cDNA samples derived from RNA isolated from primary chondrocytes of individual rib cartilages from Hoxd4 and Hoxc8 transgenic mice, respectively. RESULTS:This study shows that the Hox transgenes produce overexpression of Hoxd4 and Hoxc8 in primary chondrocytes from perinatal transgenic mice. However, no differences were found in expression levels of the folate pathway genes in transgenic cells compared to littermate controls. CONCLUSIONS:Our results provide evidence that folate pathway genes are only indirect targets of Hox transgene overexpression in our transgenic animals. These expression studies provide a baseline for future studies into the role of folate metabolism in chondrocyte differentiation.

| S-EPMC3938170 | biostudies-literature

Microarray analyses of transgenic zebrafish expressing human KIT-D816V gene versus wild-type zebrafish

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-02-03 | E-GEOD-54615 | biostudies-arrayexpress

Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-08-05 | GSE102259 | GEO

mRNA expression data from either wild-type mice or Scnn1b-transgenic mice at post-natal days 0, 3, 10, and 42.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-09-11 | E-GEOD-47551 | biostudies-arrayexpress

Differentiation defective phenotypes revealed by large scale analyses of human pluripotent stem cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series