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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

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

Journal

The Journal of clinical investigation

Publication Data

May 12, 2000

Associated Grants

None

Mesh Terms

  • 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