Defects in vestibular sensory epithelia and innervation in mice with loss of Chd7 function: Implications for human CHARGE syndrome

Meredith E. Adams, Elizabeth A. Hurd, Lisa A. Beyer, Donald L. Swiderski, Yehoash Raphael, Donna M. Martin

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

CHD7 is a chromodomain gene mutated in CHARGE syndrome, a multiple anomaly condition characterized by ocular coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, and ear defects including deafness and semi-circular canal dysgenesis. Mice with heterozygous Chd7 deficiency have circling behavior and semicircular canal defects and are an excellent animal model for exploring the pathogenesis of CHARGE features. Inner ear vestibular defects have been characterized in heterozygous Chd7-deficient embryos and early postnatal mice, but it is not known whether vestibular defects persist throughout adulthood in Chd7-deficient mice or whether the vestibular sensory epithelia and their associated innervation and function are intact. Here we describe a detailed analysis of inner ear vestibular structures in mature mice that are heterozygous for a Chd7-deficient, gene-trapped allele (Chd7 Gt/+). Chd7Gt/+ mice display variable asymmetric lateral and posterior semicircular canal malformations, as well as defects in vestibular sensory epithelial innervation despite the presence of intact hair cells in the target organs. These observations have important functional implications for understanding the clinical manifestations of CHD7 mutations in humans and for designing therapies to treat inner ear vestibular dysfunction.

Original languageEnglish (US)
Pages (from-to)519-532
Number of pages14
JournalJournal of Comparative Neurology
Volume504
Issue number5
DOIs
StatePublished - Oct 10 2007

Keywords

  • Inner ear
  • Innervation
  • Mouse mutant
  • Sensory epithelia

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