These authors contributed equally to this study.
Association between congenital defects in papillary outgrowth and functional obstruction in Crim1 mutant mice†
Article first published online: 23 MAY 2012
Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 227, Issue 4, pages 499–510, August 2012
How to Cite
Wilkinson, L., Kurniawan, N. D., Phua, Y. L., Nguyen, M. J., Li, J., Galloway, G. J., Hashitani, H., Lang, R. J. and Little, M. H. (2012), Association between congenital defects in papillary outgrowth and functional obstruction in Crim1 mutant mice. J. Pathol., 227: 499–510. doi: 10.1002/path.4036
No conflicts of interest were declared.
- Issue published online: 10 JUL 2012
- Article first published online: 23 MAY 2012
- Accepted manuscript online: 4 APR 2012 07:03AM EST
- Manuscript Accepted: 29 MAR 2012
- Manuscript Revised: 9 MAR 2012
- Manuscript Received: 9 DEC 2011
- obstructive nephropathy;
- functional obstruction;
- magnetic resonance imaging;
- pyeloureteric peristalsis
Crim1 hypomorphic (Crim1) mice display progressive renal disease characterized by glomerular defects, leaky peritubular vasculature, and progressive interstitial fibrosis. Here we show that 27% of these mice also present with hydronephrosis, suggesting obstructive nephropathy. Dynamic magnetic resonance imaging using Magnevist showed fast development of hypo-intense signal in the kidneys of Crim1 mice, suggesting pooling of filtrate within the renal parenchyma. Rhodamine dextran (10 kDa) clearance was also delayed in Crim1 mice. Pyeloureteric peristalsis, while present, was less co-ordinated in Crim1 mice. However, isolated renal pelvis preparations suggest normal pelvic smooth muscle contractile responses. An analysis of maturation during the immediate postnatal period [postnatal day (P) 0-15] revealed defects in papillary extension in Crim1 mice. While Crim1 expression is weak in pelvic smooth muscle, strong expression is seen in the interstitium and loops of Henle of the extending papilla, commencing at the tip of the P1 papilla and disseminating throughout the papilla by P15. These results, as well as implicating Crim1 in papillary extension and pelvic smooth muscle contractility, highlight the previously unrecognized association between defects in papillary development and progression to chronic kidney disease later in life. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.