Unknown,Transcriptomics,Genomics,Proteomics

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Stabilization of ß-catenin during murine Kidney Development


ABSTRACT: We define a pathogenic role for a ß-catenin-activated genetic pathway in murine renal dysplasia. Cre-mediated stabilization of ß-catenin in the ureteric cell lineage prior to the onset of kidney development increased ß-catenin levels and caused renal aplasia or severe hypodysplasia. A genome-wide analysis of mRNA expression in dysplastic tissue identified down-regulation of genes required for ureteric branching and up regulation of Tgfß2 and Dkk1. Hoxb7-Cre:EGFP mice ( Zhao, et al. (2004) Dev Biol 276:403-415) were crossed with mice containing loxP sites flanking exon 3 of the ß-catenin allele (ß-catdelta3/delta3) (Harada,et al. (2002) Cancer Res 62:1971-1977) to generate ß-catenin gain-of-function mutant mice specific to the uteric bud, termed ß-catGOF-UB .Eighteen ß-catGOF-UB mutant kidneys and 9 WT kidneys were micro-dissected at E12.5. Mutant kidneys were divided into three random pools (n=3) consisting of 6 kidneys each and mRNA expression assessed by microarray.

ORGANISM(S): Mus musculus

SUBMITTER: Brian Cox 

PROVIDER: E-GEOD-20325 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

β-catenin causes renal dysplasia via upregulation of Tgfβ2 and Dkk1.

Bridgewater Darren D   Di Giovanni Valeria V   Cain Jason E JE   Cox Brian B   Jakobson Madis M   Sainio Kirsi K   Rosenblum Norman D ND  

Journal of the American Society of Nephrology : JASN 20110324 4


Renal dysplasia, defined by defective ureteric branching morphogenesis and nephrogenesis, is the major cause of renal failure in infants and children. Here, we define a pathogenic role for a β-catenin-activated genetic pathway in murine renal dysplasia. Stabilization of β-catenin in the ureteric cell lineage before the onset of kidney development increased β-catenin levels and caused renal aplasia or severe hypodysplasia. Analysis of gene expression in the dysplastic tissue identified downregula  ...[more]

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