Deregulation of Pax-2 expression in transgenic mice generates severe kidney abnormalities.
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 man. In the developing kidney, Pax-2 is expressed in the induced mesenchyme, in the ureter epithelium, and in early epithelial structures derived from the mesenchyme. Pax-2 expression is repressed upon terminal differentiation of the renal tubule epithelium, but persists in the undifferentiated epithelium of human Wilms' tumours. 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.
Dressler
G R
GR
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Wilkinson
J E
JE
Rothenpieler
U W
UW
Patterson
L T
LT
Williams-Simons
L
L
Westphal
H
H
D000818:Animals; D001806:Blood Urea Nitrogen; D015820:Cadherins / Q000032:analysis; D003587:Cytomegalovirus / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005814:Genes, Viral; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000002:abnormalities* / Q000166:cytology / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051762:PAX2 Transcription Factor; D011188:Potassium / Q000097:blood; D011401:Promoter Regions, Genetic; D012016:Reference Values; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*
D015820:Cadherins; D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; C497319:Pax2 protein, mouse; D014157:Transcription Factors; D011188:Potassium