The inner ear phenotype of Volchok (Vlk): An ENU-induced mouse model for CHARGE syndrome

Author: Lenz Danielle R.   Dror Amiel A.   Wekselman Guy   Fuchs Helmut   de Angelis Martin Hrabé   Avraham Karen B.  

Publisher: Informa Healthcare

ISSN: 1651-386X

Source: Audiological Medicine, Vol.8, Iss.3, 2010-10, pp. : 110-119

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

AbstractObjective: The Volchok (Vlk) mouse originated as a part of a large-scale ENU program on a C3HeB/FeJ background. The mice present a dominant pattern of inheritance reflected mainly by circling activity, which led us to search for the causative mutation underlying the vestibular phenotype. Study design: Linkage analysis and subsequent sequencing were used to narrow down the genomic region and uncover the mutation, respectively. Behavioral analysis and examination of the inner ear phenotype was performed using the modified SHIRPA protocol, auditory brainstem response (ABR), immunofluorescence, light microscopy, scanning electron microscopy (SEM), paint-fill and neurofilament staining techniques. Results: A nonsense mutation was discovered in the Chd7 gene responsible for CHARGE syndrome in humans, which leads to a decrease in Chd7 expression in the nuclei of the vestibular and cochlear cells and structural abnormalities in the inner ear. A mild hearing loss was found in the mutant mice. The malformations detected include a truncated lateral semicircular canal and smaller lateral crista, a decrease in size or absence of the round window in the cochlea and lack of innervations to the posterior crista. Conclusion: Vlk joins a series of previously characterized mice bearing a Chd7 mutation, linking abnormalities found both in ENU-induced mutants and a knock-out mouse model. Combining the information from multiple Chd7 alleles provides a more comprehensive understanding of the mechanisms underlying this human disease.