Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2beta.
Expression of AP-2 transcription factors has been detected previously in embryonic renal tissues. We show here that AP-2beta -/- mice complete embryonic development and die at postnatal days 1 and 2 because of polycystic kidney disease. Analyses of kidney development revealed that induction of epithelial conversion, mesenchyme condensation, and further glomerular and tubular differentiation occur normally in AP-2beta-deficient mice. At the end of embryonic development expression of bcl-X(L), bcl-w, and bcl-2 is down-regulated in parallel to massive apoptotic death of collecting duct and distal tubular epithelia. Addressing the molecular mechanism we show that transfection of AP-2 into cell lines in vitro strongly suppresses c-myc-induced apoptosis pointing to a function of AP-2 in programming cell survival during embryogenesis. The position of the human AP-2beta gene was identified at chromosome 6p12-p21.1, within a region that has been mapped for autosomal recessive polycystic kidney disease (ARPKD). Sequence analyses of ARPKD patients and linkage analyses using intragenic polymorphic markers indicate that the AP-2beta gene is located in close proximity to but distinct from the ARPKD gene.
Pubmed ID: 9271117 RIS Download
Animals | Apoptosis | Cells, Cultured | Chromosome Mapping | Chromosomes, Human, Pair 6 | DNA-Binding Proteins | Embryonic and Fetal Development | Epithelial Cells | Gene Expression Regulation, Developmental | Genes, myc | Genetic Linkage | Humans | Kidney | Kidney Tubules | Mice | Mice, Knockout | Molecular Sequence Data | Phenotype | Polycystic Kidney, Autosomal Recessive | Restriction Mapping | Sequence Analysis, DNA | Transcription Factor AP-2 | Transcription Factors