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

J Clin Invest. 2000 May;105(10):1345-52. doi: 10.1172/JCI8635.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Disintegrins
  • ADAM Proteins
  • ADAMTS1 Protein
  • ADAMTS1 protein, human
  • Adamts1 protein, mouse
  • Metalloendopeptidases