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Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2beta.

ABSTRACT: 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.

SUBMITTER: Moser M

PROVIDER: S-EPMC316415 | biostudies-literature | 1997 Aug

REPOSITORIES: biostudies-literature

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Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2beta.

Moser M M Pscherer A A Roth C C Becker J J Mücher G G Zerres K K Dixkens C C Weis J J Guay-Woodford L L Buettner R R Fässler R R

Genes & development 19970801 15

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 ...[more]

PMID: 9271117

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Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2beta.

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Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2beta.

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