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Nephrol Dial Transplant (2002) 17: 39-41
© 2002 European Renal Association-European Dialysis and Transplant Association

Congenital Anomalies of the Kidney and Urinary Tract

A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-1 null mutant mice develop renal lesions mimicking obstructive nephropathy

Hitoshi Yokoyama, Takashi Wada, Ken-ichi Kobayashi, Kouji Kuno1, Hiroki Kurihara2, Takayuki Shindo3 and Kouji Matsushima4

Division of Blood Purification, Department of Gastroenterology and Nephrology, Graduate School of Medicine and 1 Department of Molecular Pharmacology, Cancer Research Institute, Kanazawa University, Kanazawa, 2 Department of Embryogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, 3 Department of Cardiovascular Medicine and 4 Department of Molecular Preventive Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

Abstract

Background. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-1 is distinguished from other a disintegrin and metalloproteinase molecules by the presence of thrombospondin type 1 motifs at its C-terminus and anchors to the extracellular matrix. We studied the biological role of ADAMTS-1 in the kidney.

Methods. We developed ADAMTS-1 null mice by replacing exons 2–4, which encode most of the metalloproteinase domain, with the neomycin resistance gene.

Results. In normal mice, ADAMTS-1 was detected in the epithelial cells of collecting ducts, and more intensely in the urinary epithelium at the ureteropelvic junction in kidney. We found that targeted disruption of the mouse ADAMTS-1 gene resulted in enlarged renal calices accompanied by bilateral hydronephrosis and papillary atrophy ~4 weeks after birth. Electron microscopic examination revealed the fibrotic changes and hypervascularity of capillaries between the urinary epithelial cell layer and smooth muscle cell layer at the ureteropelvic junction.

Conclusion. ADAMTS-1 appears necessary for normal kidney morphology and function. Moreover, the resemblance of the renal phenotype to human ureteropelvic junction obstruction may provide a clue to the pathogenesis of this common congenital disease.

Keywords: ADAMTS-1; hydronephrosis; ureteropelvic junction obstruction

Notes

Correspondence and offprint requests to: Hitoshi Yokoyama, MD, PhD, Division of Blood Purification, Department of Gastroenterology and Nephrology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Japan.


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