Beta1-integrin is required for kidney collecting duct morphogenesis and maintenance of renal function.
Deletion of integrin-beta1 (Itgb1) in the kidney collecting system led to progressive renal dysfunction and polyuria. The defect in the concentrating ability of the kidney was concomitant with decreased medullary collecting duct expression of aquaporin-2 and arginine vasopressin receptor 2, while histological examination revealed hypoplastic renal medullary collecting ducts characterized by increased apoptosis, ectasia and cyst formation. In addition, a range of defects from small kidneys with cysts and dilated tubules to bilateral renal agenesis was observed. This was likely due to altered growth and branching morphogenesis of the ureteric bud (the progenitor tissue of the renal collecting system), despite the apparent ability of the ureteric bud-derived cells to induce differentiation of the metanephric mesenchyme. These data not only support a role for Itgb1 in the development of the renal collecting system but also raise the possibility that Itgb1 links morphogenesis to terminal differentiation and ultimately collecting duct function and/or maintenance.
Department of Pediatrics, University of California, La Jolla, California 92093-0693, USA.
Wei
W
Wu
Shinji
S
Kitamura
David M
DM
Truong
Timo
T
Rieg
Volker
V
Vallon
Hiroyuki
H
Sakurai
Kevin T
KT
Bush
David R
DR
Vera
Robert S
RS
Ross
Sanjay K
SK
Nigam
D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D004195:Disease Models, Animal; D005838:Genotype; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000196:embryology* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D017483:Receptors, Vasopressin / Q000378:metabolism; D051437:Renal Insufficiency / Q000235:genetics
C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; D019012:Integrin beta1; D017483:Receptors, Vasopressin