Mice with cav-1 gene disruption have benign stromal lesions and compromised epithelial differentiation

Exp Mol Pathol. 2008 Apr;84(2):131-40. doi: 10.1016/j.yexmp.2007.08.004. Epub 2007 Aug 31.


Caveolin-1 (cav-1) is a major structural protein of caveolae, small invaginations of the plasma membrane that integrate and regulate signaling pathways involved in cell growth and differentiation. We previously generated a genetically engineered mice that are homozygous for a null mutation in exon 2 of cav-1 and documented increased incidence of urolithiasis in young male cav-1(-/-) mice. We attributed this, in part, to improper localization of plasma membrane calcium/calmodulin-dependent calcium ATPase in the distal convoluted tubules of the kidney. To document pathologies related to cav-1 function, we maintained cav-1(-/-) and control cav-1(+/+) mice for an extended time period. We report here that cav-1(-/-) mice demonstrate organ-specific growth-related disorders in stromal cells that normally have high levels of cav-1 expression. In many of these organs, epithelial cell growth/differentiation abnormalities were also observed, yet in most of these sites the epithelial cells normally express low to non-detectable levels of cav-1. We propose that loss of cav-1 function in stromal cells of various organs directly leads to a disorganized stromal compartment that, in turn, indirectly promotes abnormal growth and differentiation of adjacent epithelium.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Caveolin 1 / genetics*
  • Caveolin 1 / metabolism
  • Cell Differentiation
  • Epithelial Cells / cytology*
  • Epithelial Cells / physiology
  • Female
  • Gene Expression Regulation / physiology*
  • Gene Silencing*
  • Genitalia / metabolism
  • Genitalia / pathology
  • Keratins / metabolism
  • Longevity
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Animal / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pancreas / metabolism
  • Pancreas / pathology
  • Spleen / metabolism
  • Spleen / pathology
  • Stromal Cells / cytology
  • Stromal Cells / physiology
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology


  • Biomarkers
  • Caveolin 1
  • Keratins