101. Disruption of the Caveolin-1 Gene Impairs Renal Calcium Reabsorption and Leads to Hypercalciuria and Urolithiasis
- Author
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Timothy B. Boone, Guangwen Cao, Nobuyuki Kusaka, Chengzhen Ren, Alexei A. Goltsov, Terry L. Timme, Takashi Saika, Timothy C. Thompson, Taoyan Men, Hongyu Wang, Dov Kadmon, Weihua Tian, Luan D. Truong, Takefumi Satoh, Guang Yang, Allan Bradley, A. Craig Chinault, Wei Wen Cai, and Sanghee Park
- Subjects
medicine.medical_specialty ,Caveolin 1 ,Restriction Mapping ,chemistry.chemical_element ,Calcium ,Biology ,Kidney ,Caveolins ,Polymerase Chain Reaction ,Pathology and Forensic Medicine ,Mice ,Calcium Metabolism Disorders ,Internal medicine ,medicine ,Animals ,Hypercalciuria ,Distal convoluted tubule ,DNA Primers ,Mice, Knockout ,Calcium metabolism ,Reabsorption ,Exons ,medicine.disease ,Urinary calcium ,Disease Models, Animal ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Creatinine ,Plasma membrane Ca2+ ATPase ,Urinary Calculi ,Regular Articles - 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.
- Published
- 2003
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