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

T Shindo1, H Kurihara, K Kuno

  • 1Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

The Journal of Clinical Investigation
|May 17, 2000
PubMed

Insights

The study found that ADAMTS-1 is essential for normal growth, fertility, and organ development. Mice lacking ADAMTS-1 exhibited growth retardation, reproductive issues, and kidney abnormalities, suggesting its critical role in physiological functions.

Area of Science:

  • Biochemistry
  • Genetics
  • Developmental Biology

Background:

  • A disintegrin and metalloproteinase (ADAM) proteins are crucial enzymes involved in various biological processes.
  • ADAMTS-1, a specific member, possesses unique structural features including thrombospondin type I motifs and extracellular matrix anchoring.
  • Its precise biological functions remained largely unelucidated prior to this study.

Purpose of the Study:

  • To investigate the in vivo biological role of ADAMTS-1.
  • To characterize the physiological consequences of ADAMTS-1 deficiency.

Main Methods:

  • Gene targeting was employed to generate ADAMTS-1-null mice.
  • Phenotypic analysis of the generated knockout mice was performed, including assessments of growth, fertility, and organ morphology.

Main Results:

  • ADAMTS-1-null mice displayed significant growth retardation and adipose tissue malformation.
  • Impaired female fertility was observed, with associated histological changes in reproductive organs.
  • Enlarged renal calices, ureteropelvic junction fibrosis, and abnormal adrenal medullary architecture were prominent findings in knockout mice.

Conclusions:

  • ADAMTS-1 is indispensable for normal mammalian growth, reproductive capacity, and the morphological and functional integrity of key organs.
  • The observed renal phenotype in ADAMTS-1-null mice offers potential insights into the pathogenesis of human ureteropelvic junction obstruction.

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