期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 105, 期 10, 页码 1345-1352出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI8635
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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.
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