• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Expression of R120G-alphaB-crystallin causes aberrant desmin and alphaB-crystallin aggregation and cardiomyopathy in mice.

Upregulation of alphaB-crystallin (CryAB), a small heat shock protein, is associated with a variety of diseases, including the desmin-related myopathies. CryAB, which binds to both desmin and cytoplasmic actin, may participate as a chaperone in intermediate filament formation and maintenance, but the physiological consequences of CryAB upregulation are unknown. A mutation in CryAB, R120G, has been linked to a familial desminopathy. However, it is unclear whether the mutation is directly causative. We created multiple transgenic mouse lines that overexpressed either murine wild-type CryAB or the R120G mutation in cardiomyocytes. Overexpression of wild-type CryAB was relatively benign, with no increases in mortality and no induction of desmin-related cardiomyopathy even in a line in which CryAB mRNA expression was increased approximately 104-fold and the protein level increased by 11-fold. In contrast, lines expressing the R120G mutation were compromised, with a high-expressing line exhibiting 100% mortality by early adulthood. Modest expression levels resulted in a phenotype that was strikingly similar to that observed for the desmin-related cardiomyopathies. The desmin filaments in the cardiomyocytes were overtly affected, myofibril alignment was significantly impaired, and a hypertrophic response occurred at both the molecular and cellular levels. The data show that the R120G mutation causes a desminopathy, is dominant negative, and results in cardiac hypertrophy.

Pubmed ID: 11440982


  • Wang X
  • Osinska H
  • Klevitsky R
  • Gerdes AM
  • Nieman M
  • Lorenz J
  • Hewett T
  • Robbins J


Circulation research

Publication Data

July 6, 2001

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL41496
  • Agency: NHLBI NIH HHS, Id: HL52318
  • Agency: NHLBI NIH HHS, Id: HL56370
  • Agency: NHLBI NIH HHS, Id: HL56620
  • Agency: NHLBI NIH HHS, Id: HL60546
  • Agency: NHLBI NIH HHS, Id: HL62459

Mesh Terms

  • Animals
  • Cardiomegaly
  • Crystallins
  • Desmin
  • Mice
  • Mice, Transgenic
  • Mutation, Missense
  • Myocardial Contraction
  • Myocardium
  • RNA, Messenger
  • Survival Rate