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

A disintegrin and metalloproteinase (ADAM) represents a protein family poss essing both metalloproteinase and disintegrin domains. ADAMTS-1, an ADAM fa mily member cloned from cachexigenic colon adenocarcinoma, is unusual in th at it contains thrombospondin type I motifs and anchors to the extracellula r 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 g ene resulted in growth retardation with adipose tissue malformation, Impair ed female fertilization accompanied by histological changes in the uterus a nd ovaries also resulted, Furthermore, ADAMTS-1(-/-) mice demonstrated enla rged renal calices with fibrotic changes from the ureteropelvic junction th rough the ureter, and abnormal adrenal medullary architecture without capil lary formation. ADAMTS-1 thus appears necessary for normal growth, fertilit y, and organ morphology and function. Moreover, the resemblance of the rena l phenotype to human ureteropelvic junction obstruction may provide a clue to the pathogenesis of this common congenital disease.