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(American Journal of Pathology. 2000;157:833-842.)
© 2000 American Society for Investigative Pathology

Regular Articles

PAX2 Suppresses Apoptosis in Renal Collecting Duct Cells

Elena Torban^*, Michael Roger Eccles^*, Jack Favor and Paul Rowland Goodyer^*

From the Departments of Pediatrics and Experimental Medicine,^*
McGill University, Montreal, Quebec, Canada; the Cancer Genetics Laboratory,
Department of Biochemistry, University of Otago, Dunedin, New Zealand; and the GSF-National Research Center for Environmental Health,
Institute of Mammalian Genetics, Neuherberg, Germany

PAX2 is a transcription factor belonging to the evolutionarily conserved paired box family and is required during development of the central nervous system and genitourinary axis. Mutations in the PAX2 gene cause a rare autosomal dominant renal-coloboma syndrome, characterized by optic nerve colobomas and renal hypoplasia. Recent analysis of a spontaneous PAX2 mutant mouse model (1Neu) revealed that the major cause of renal hypoplasia is reduced branching of the ureteric bud (UB) and fewer nephrons. We have observed that this abnormality is associated with a striking increase in the number of UB cells undergoing programmed cell death during nephrogenesis. To ascertain whether apoptosis is directly linked to the level of PAX2 expression, we have studied the role of PAX2 in cultured renal cells. We show that mIMCD-3 cells, a murine collecting duct cell line with high endogenous PAX2 expression, undergo apoptosis when transfected with anti-sense PAX2. In contrast, HEK293 cells expressing exogenous PAX2 are protected against apoptotic death induced by caspase-2. PAX2 has no effect on proliferation of embryonic kidney or in cultured kidney cells. Our observations imply a direct role for PAX2 in survival of ureteric bud cells.

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