ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function

• Published in: The Journal of clinical investigation Vol. 105; no. 10; pp. 1345 - 1352
• Main Authors: Shindo, T, Kurihara, H, Kuno, K, Yokoyama, H, Wada, T, Kurihara, Y, Imai, T, Wang, Y, Ogata, M, Nishimatsu, H, Moriyama, N, Oh-hashi, Y, Morita, H, Ishikawa, T, Nagai, R, Yazaki, Y, Matsushima, K
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.05.2000
• Subjects: ADAM Proteins; ADAMTS1 Protein; Adrenal Glands - abnormalities; Animals; Disintegrins - chemistry; Disintegrins - genetics; Disintegrins - physiology; Female; Fertility - genetics; Fertility - physiology; Growth - genetics; Growth - physiology; Humans; Infertility, Female - etiology; Kidney - abnormalities; Male; Metalloendopeptidases - chemistry; Metalloendopeptidases - genetics; Metalloendopeptidases - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovary - abnormalities; Phenotype; Pregnancy; Uterus - abnormalities
• ISSN: 0021-9738
• DOI: 10.1172/JCI8635

A disintegrin and metalloproteinase (ADAM) represents a protein family possessing both metalloproteinase and disintegrin domains. ADAMTS-1, an ADAM family member cloned from cachexigenic colon adenocarcinoma, is unusual in that it contains thrombospondin type I motifs and anchors to the extracellular matrix. To elucidate the biological role of ADAMTS-1, we developed ADAMTS-1-null mice by gene targeting. Targeted disruption of the mouse ADAMTS-1 gene resulted in growth retardation with adipose tissue malformation. Impaired female fertilization accompanied by histological changes in the uterus and ovaries also resulted. Furthermore, ADAMTS-1(-/-) mice demonstrated enlarged renal calices with fibrotic changes from the ureteropelvic junction through the ureter, and abnormal adrenal medullary architecture without capillary formation. ADAMTS-1 thus appears necessary for normal growth, fertility, and organ 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.