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Defects in vestibular sensory epithelia and innervation in mice with loss of Chd7 function: Implications for human CHARGE syndrome
Author(s) -
Adams Meredith E.,
Hurd Elizabeth A.,
Beyer Lisa A.,
Swiderski Donald L.,
Raphael Yehoash,
Martin Donna M.
Publication year - 2007
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.21460
Subject(s) - charge syndrome , biology , vestibular system , inner ear , posterior semicircular canal , anatomy , dysgenesis , semicircular canal , saccule , hearing loss , sensory system , coloboma , neuroscience , audiology , medicine , genetics
CHD7 is a chromodomain gene mutated in CHARGE syndrome, a multiple anomaly condition characterized by ocular c oloboma, h eart defects, a tresia of the choanae, r etarded growth and development, g enital hypoplasia, and e ar defects including deafness and semicircular 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/+ ). Chd7 Gt/+ 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. J. Comp. Neurol. 504:519–532, 2007. © 2007 Wiley‐Liss, Inc.