Calcineurin is required in urinary tract mesenchyme for the development of the pyeloureteral peristaltic machinery

Ching Pin Chang, Bradley W. McDill, Joel R. Neilson, Heidi E. Joist, Jonathan A. Epstein, Gerald R. Crabtree, Feng Chen

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

Congenital obstructive nephropathy is the principal cause of renal failure in infants and children. The underlying molecular and cellular mechanisms of this disease, however, remain largely undetermined. We generated a mouse model of congenital obstructive nephropathy that resembles ureteropelvic junction obstruction in humans. In these mice, calcineurin function is removed by the selective deletion of Cnb1 in the mesenchyme of the developing urinary tract using the Cre/lox system. This deletion results in reduced proliferation in the smooth muscle cells and other mesenchymal cells in the developing urinary tract. Compromised cell proliferation causes abnormal development of the renal pelvis and ureter, leading to defective pyeloureteral peristalsis, progressive renal obstruction, and, eventually, fatal renal failure. Our study demonstrates that calcineurin is an essential signaling molecule in urinary tract development and is required for normal proliferation of the urinary tract mesenchymal cells in a cell-autonomous manner. These studies also emphasize the importance of functional obstruction, resulting from developmental abnormality, in causing congenital obstructive nephropathy.

Original languageEnglish (US)
Pages (from-to)1051-1058
Number of pages8
JournalJournal of Clinical Investigation
Volume113
Issue number7
DOIs
StatePublished - Apr 2004

ASJC Scopus subject areas

  • Medicine(all)

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    Chang, C. P., McDill, B. W., Neilson, J. R., Joist, H. E., Epstein, J. A., Crabtree, G. R., & Chen, F. (2004). Calcineurin is required in urinary tract mesenchyme for the development of the pyeloureteral peristaltic machinery. Journal of Clinical Investigation, 113(7), 1051-1058. https://doi.org/10.1172/JCI20049