title: Association between congenital defects in papillary outgrowth and functional obstruction in Crim1 mutant mice.
abstract: Crim1 hypomorphic (Crim1(KST264/KST264)) 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(KST264/KST264) mice, suggesting pooling of filtrate within the renal parenchyma. Rhodamine dextran (10 kDa) clearance was also delayed in Crim1(KST264/KST264) mice. Pyeloureteric peristalsis, while present, was less co-ordinated in Crim1(KST264/KST264) 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({KST264/KST264) 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.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, QLD 4072, Australia.
authors.forename: Lorine
authors.initials: L
authors.lastname: Wilkinson
authors.forename: Nyoman D
authors.initials: ND
authors.lastname: Kurniawan
authors.forename: Yu Leng
authors.initials: YL
authors.lastname: Phua
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Nguyen
authors.forename: Joan
authors.initials: J
authors.lastname: Li
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Galloway
authors.forename: Hikaru
authors.initials: H
authors.lastname: Hashitani
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lang
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Little
mesh_terms: D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000235:genetics* / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism; D006869:Hydronephrosis / Q000151:congenital* / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000151:congenital* / Q000378:metabolism / Q000503:physiopathology; D007679:Kidney Medulla / Q000002:abnormalities* / Q000378:metabolism / Q000503:physiopathology*; D008138:Loop of Henle / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009119:Muscle Contraction / Q000502:physiology; D009154:Mutation / Q000235:genetics*; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D012235:Rhodamines / Q000378:metabolism
chemical_list: C518411:Crim1 protein, mouse; D003911:Dextrans; D012235:Rhodamines; C051311:rhodamine dextran; D052004:Bone Morphogenetic Protein Receptors