Abstract
THE Pax genes comprise a family of transcription factors active in specific tissues during embryonic development and are associated with at least three developmental mutations in mouse and man1,2. In the developing kidney, Pax-2 is expressed in the induced mesenchyme, in the ureter epithelium, and in early epithelial structures derived from the mesenchyme3. Pax-2 expression is repressed upon terminal differentiation of the renal tubule epithelium, but persists in the undifferentiated epithelium of human Wilms' tumours4,5. We have produced a dominant gain-of-function mutation in transgenic mice by deregulating the expression of the mouse Pax-2 gene. The data obtained with four independently derived transgenic embryos and with one transgenic line demonstrate that deregulated Pax-2 expression results in histologically abnormal and dysfunctional renal epithelium with properties similar to congenital nephrotic syndrome. Thus, repression of Pax-2 is required for normal kidney development and persistent expression of Pax-2 may restrict the differentiation potential of renal epithelial cells.
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References
Walther, C. et al. Genomics 11, 424–434 (1991).
Gruss, P. & Walther, C. Cell 69, 719–722 (1992).
Dressler, G. R., Deutsch, U., Chowdhury, K., Nornes, H. O. & Gruss, P. Development 109, 787–795 (1990).
Dressler, G. R. & Douglass, E. C. Proc. natn. Acad. Sci. U.S.A. 89, 1179–1183 (1992).
Eccles, M. R. et al. Cell Growth Differ. 3, 279–289 (1992).
Saxen, L. Organogenesis of the Kidney. Developmental and Cell Biology Series (eds Barlow, P. W., Green, P. B. & White, C. C.) (Cambridge Univ. Press, Cambridge, 1987).
Foecking, M. K. & Hofstetter, H. Gene 45, 101–105 (1986).
Furth, P. A., Hennighausen, L., Baker, C. Beatty, B. & Woychick, R. Nucleic Acids Res. 25, 6205–6208 (1991).
Nornes, H. O., Dressler, G. R., Knapik, E. W., Deutsch, U. & Gruss, P. Development 109, 797–809 (1990).
Pueschel, A., Westerfield, M. & Dressler, G. R. Mech. Dev. 38, 197–208 (1992).
Vestweber, D. & Kemler, R. EMBO J. 4, 3393–3398 (1985).
Mahan, J. D. & Vernier, R. L. in Pediatric Nephrology (eds Holliday, M. A., Barratt, T. M. & Vernier, R. L.)(Williams & Wllkins, Baltimore, 1987).
Gorman, C. M., Merlino, G. T., Willingham, M. C., Pastan, I. & Howard, B. H. Proc. natn. Acad. Sci. U.S.A. 79, 6777–6781 (1982).
Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1989).
Overbeek, P. A., Chepelinsky, A. B., Khillian, J. S., Piatigorsky, J. & Westphal, H. Proc. natn. Acad. Sci. U.S.A. 82, 7815–7819 (1985).
Hogan, B., Constantini, F. & Lacy, E. Manipulating the Mouse Embryo: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1986).
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Dressler, G., Wilkinson, J., Rothenpieler, U. et al. Deregulation of Pax-2 expression in transgenic mice generates severe kidney abnormalities. Nature 362, 65–67 (1993). https://doi.org/10.1038/362065a0
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DOI: https://doi.org/10.1038/362065a0
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