Partially redundant functions of Adamts1 and Adamts4 in the perinatal development of the renal medulla

Dev Dyn. 2011 Jul;240(7):1806-14. doi: 10.1002/dvdy.22662. Epub 2011 May 16.

Abstract

Adamts4 encodes a widely-expressed proteinase thought to be involved in processes ranging from cartilage metabolism to ovarian follicle development. To study its physiological roles, Adamts4-null mice were created by gene targeting. Unexpectedly, these were found to be phenotypically normal, suggesting that other gene(s) may compensate for its loss. Adamts4(-/-) mice were, therefore, crossed with a strain lacking Adamts1, whose pattern of expression and substrate specificity overlap that of Adamts4. Most (>95%) Adamts1(-/-) ;Adamts4(-/-) mice died within 72 hr after birth with a marked thinning of the renal medulla. The renal defect was not observed in embryonic Adamts1(-/-) ;Adamts4(-/-) kidneys, but became apparent around birth. The few (<5%) Adamts1(-/-) ;Adamts4(-/-) animals to reach adulthood had the same renal phenotype seen in newborns. This study is thus the first to report Adamts4 expression and function in the mammalian kidney, and to demonstrate that Adamts1 and Adamts4 play redundant and essential roles in perinatal kidney development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism*
  • ADAMTS1 Protein
  • ADAMTS4 Protein
  • Animals
  • Blotting, Western
  • Female
  • Immunohistochemistry
  • Kidney Medulla / embryology*
  • Kidney Medulla / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Procollagen N-Endopeptidase / genetics
  • Procollagen N-Endopeptidase / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • ADAM Proteins
  • ADAMTS1 Protein
  • Adamts1 protein, mouse
  • Procollagen N-Endopeptidase
  • ADAMTS4 Protein
  • Adamts4 protein, mouse