title: Desmin filaments and cardiac disease: establishing causality.
abstract: BACKGROUND
  Gene targeting studies indicate that desmin is not required for embryonic myogenesis and heart formation but is essential for maintaining the structural and functional integrity of myocytes. Desmin-null mouse hearts developed hypertrophy and dilatation. However, the expression of desmin is very often upregulated rather than downregulated in many cardiac diseases. Altered distribution of desmin protein has been observed in dilated cardiomyopathy, as well as desminopathies to which a number of mutations of desmin and a missense mutation of alphaB-crystallin (CryAB) have been linked.
  
  
  RESULTS
  Using mouse transgenesis, we have recently demonstrated that modest overexpression of a mutant form of either desmin or CryAB in the heart leads to aberrant aggregation of desmin and CryAB proteins, disruption of the normal desmin network, perturbation of myofibril alignment, and distortion of the nuclear shape. The transgenic hearts develop concentric cardiac hypertrophy and diastolic malfunction at the early stage and ventricular dilatation and congestive heart failure subsequently. Moderate overexpression of either wild-type protein, however, did not cause discernible morphological and functional abnormalities or increased mortality.
  
  
  CONCLUSIONS
  Thus cardiac overexpression of wild-type desmin is not detrimental whereas aberrant aggregation of desmin and disruption of the desmin network remodel the heart and compromise cardiac function.
authors.affiliation: Division of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Wang
authors.forename: Hanna
authors.initials: H
authors.lastname: Osinska
authors.forename: A Martin
authors.initials: AM
authors.lastname: Gerdes
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Robbins
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000209:etiology; D003893:Desmin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006331:Heart Diseases / Q000209:etiology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D032383:Myocytes, Cardiac / Q000502:physiology; D018754:Ventricular Dysfunction / Q000209:etiology; D038203:alpha-Crystallin B Chain / Q000235:genetics
chemical_list: D003893:Desmin; D038203:alpha-Crystallin B Chain