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

Objective: 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 refl ected mainly by circling activity, which led us to search for the causative mutation underlying the vestibular phenotype. Study desi...

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Publicado en:Audiological Medicine Vol. 8; no. 3; pp. 110 - 120
Autores principales: Lenz, Danielle R., Dror, Amiel A., Wekselman, Guy, Fuchs, Helmut, de Angelis, Martin Hrabé, Avraham, Karen B.
Formato: pictorial research tables/charts Journal Article
Publicado: Taylor & Francis Ltd 2010
Acceso en línea:Ver este registro en EBSCOhost
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      pub: Taylor & Francis Ltd
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        atl: The inner ear phenotype of Volchok (Vlk): an ENU-induced mouse model for CHARGE syndrome.
      aug:
        au:
          Lenz, Danielle R.
          Dror, Amiel A.
          Wekselman, Guy
          Fuchs, Helmut
          de Angelis, Martin Hrabé
          Avraham, Karen B.
        affil: Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Karena@post.tau.ac.il
      sug:
        subj:
          CHARGE Syndrome
          Ear, Inner
          Hearing Disorders
          Phenotype
          Animal Studies
          Cochlea
          Funding Source
          Mice
          Microscopy, Electron, Scanning
          Models, Biological
          Research Methodology
          Vestibule, Labyrinth
      ab: Objective: 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 refl ected 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 modifi ed SHIRPA protocol, auditory brainstem response (ABR), immunofl uorescence, light microscopy, scanning electron microscopy (SEM), paint-fi ll and neurofi lament 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.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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