title: Disruption of the caveolin-1 gene impairs renal calcium reabsorption and leads to hypercalciuria and urolithiasis.
abstract: Using LoxP/Cre technology, we generated a knockout mouse homozygous for a null mutation in exon 2 of Cav1. In male Cav1-/- animals, we observed a dramatic increase in the incidence of urinary calcium stone formation. In 5-month-old male mice, the incidence of early urinary calculi was 67% in Cav1-/- mice compared to 19% in Cav1+/+ animals. Frank stone formation was observed in 13% of Cav1-/- males but was not seen in Cav1+/+ mice. Urine calcium concentration was significantly higher in Cav1-/- male mice compared to Cav1+/+ mice. In Cav1-/- mice, distal convoluted tubule cells were completely devoid of Cav1 and the localization of plasma membrane calcium ATPase was disrupted. Functional studies confirmed that active calcium absorption was significantly reduced in Cav1-/- compared to Cav1+/+ male mice. These results demonstrate that disruption of the Cav1 gene promotes the progressive steps required for urinary calcium stone formation and establish a new mouse model for urinary stone disease.
authors.affiliation: Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Cao
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Terry L
authors.initials: TL
authors.lastname: Timme
authors.forename: Takashi
authors.initials: T
authors.lastname: Saika
authors.forename: Luan D
authors.initials: LD
authors.lastname: Truong
authors.forename: Takefumi
authors.initials: T
authors.lastname: Satoh
authors.forename: Alexei
authors.initials: A
authors.lastname: Goltsov
authors.forename: Sang Hee
authors.initials: SH
authors.lastname: Park
authors.forename: Taoyan
authors.initials: T
authors.lastname: Men
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kusaka
authors.forename: Weihua
authors.initials: W
authors.lastname: Tian
authors.forename: Chengzhen
authors.initials: C
authors.lastname: Ren
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wang
authors.forename: Dov
authors.initials: D
authors.lastname: Kadmon
authors.forename: Wei Wen
authors.initials: WW
authors.lastname: Cai
authors.forename: A Craig
authors.initials: AC
authors.lastname: Chinault
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Boone
authors.forename: Allan
authors.initials: A
authors.lastname: Bradley
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Thompson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000652:urine*; D002128:Calcium Metabolism Disorders / Q000235:genetics / Q000473:pathology*; D051242:Caveolin 1; D022461:Caveolins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D003404:Creatinine / Q000652:urine; D017931:DNA Primers; D004195:Disease Models, Animal; D005091:Exons; D007668:Kidney / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D014545:Urinary Calculi / Q000235:genetics / Q000473:pathology*
chemical_list: C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D017931:DNA Primers; D003404:Creatinine; D002118:Calcium