Pax2 in development and renal disease.
Pax genes are associated with a variety of developmental mutations in mouse and man that are gene dosage sensitive, or haploinsufficient. The Pax2 gene encodes a DNA binding, transcription factor whose expression is essential for the development of the renal epithelium. Both gain and loss of function mutants in the mouse demonstrate a requirement for Pax2 in the conversion of metanephric mesenchymal precursor cells to the fully differentiated tubular epithelium of the nephron. However, Pax2 expression is down-regulated as cells leave the mitotic cycle. Humans carrying a single Pax2 mutant allele exhibit renal hypoplasia, vesicoureteric reflux, and optic nerve colobomas. Conversely, persistent expression of Pax2 has been demonstrated in a variety of cystic and dysplastic renal diseases and correlates with continued proliferation of renal epithelial cells. Thus, Pax2 misexpresssion may be a key determinant in the initiation and progression of renal diseases marked by increased or deregulated cell proliferation.
Dressler
G R
GR
Department of Pathology, The University of Michigan Medical Center, Ann Arbor 48109-0650, USA. dressler@umich.edu
Woolf
A S
AS
D000818:Animals; D003103:Coloboma / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007668:Kidney / Q000002:abnormalities* / Q000196:embryology*; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D051762:PAX2 Transcription Factor; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; C497319:Pax2 protein, mouse; D014157:Transcription Factors