Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2β
- Markus Moser1,
- Armin Pscherer1,
- Christina Roth1,
- Jutta Becker2,
- Gabi Mücher2,
- Klaus Zerres2,
- Christa Dixkens3,
- Joachim Weis4,
- Lisa Guay-Woodford5,
- Reinhard Buettner1,7, and
- Reinhard Fässler6
- 1Institute for Pathology, University of Regensburg Medical School, D-93042 Regensburg, Germany; 2Institute for Human Genetics, University of Bonn, D-53111 Bonn, Germany; 3Department of Medical Genetics, University of Ulm, D-89069 Ulm, Germany; 4Institute for Neuropathology, Rheinisch Westfaelische Technische Hochschule (RWTH) Aachen, D-52057 Aachen, Germany; 5Departments of Medicine and Pediatrics, University of Alabama, Birmingham, Alabama 35294 USA; 6Max-Planck-Institute for Biochemistry, D-82152 Martinsried, Germany
Abstract
Expression of AP-2 transcription factors has been detected previously in embryonic renal tissues. We show here thatAP-2β −/− 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-2β-deficient mice. At the end of embryonic development expression of bcl-XL, 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-2β 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-2β gene is located in close proximity to but distinct from the ARPKD gene.
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Footnotes
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↵7 Corresponding author.
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E-MAIL reinhart.buettner{at}klinik.uni-regensburg.de; FAX (49) 941-944-6602.
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- Received February 17, 1997.
- Accepted June 13, 1997.
- Cold Spring Harbor Laboratory Press
