Strain-specific hyperkyphosis and megaesophagus in Add1 null mice

Genesis. 2012 Dec;50(12):882-91. doi: 10.1002/dvg.22342. Epub 2012 Sep 12.

Abstract

The three adducin proteins (α, β, and γ) share extensive sequence, structural, and functional homology. Heterodimers of α- and β-adducin are vital components of the red cell membrane skeleton, which is required to maintain red cell elasticity and structural integrity. In addition to anemia, targeted deletion of the α-adducin gene (Add1) reveals unexpected, strain-dependent non-erythroid phenotypes. On an inbred 129 genetic background, Add1 null mice show abnormal inward curvature of the cervicothoracic spine with complete penetrance. More surprisingly, a subset of 129-Add1 null mice develop severe megaesophagus, while examination of peripheral nerves reveals a reduced number of axons in 129-Add1 null mice at four months of age. These unforeseen phenotypes, described here, reveal new functions for adducin and provide new models of mammalian disease.

Publication types

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

MeSH terms

  • Animals
  • Calmodulin-Binding Proteins / genetics*
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Esophageal Achalasia / genetics*
  • Esophageal Achalasia / pathology
  • Gene Deletion
  • Kyphosis / genetics*
  • Kyphosis / pathology
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Penetrance
  • Species Specificity

Substances

  • Add1 protein, mouse
  • Calmodulin-Binding Proteins
  • Cytoskeletal Proteins
  • adducin