ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function.
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.
Pubmed ID: 10811842 RIS Download
ADAM Proteins | Adrenal Glands | Animals | Disintegrins | Female | Fertility | Growth | Humans | Infertility, Female | Kidney | Male | Metalloendopeptidases | Mice | Mice, Inbred C57BL | Mice, Knockout | Ovary | Phenotype | Pregnancy | Uterus