| First Author | Zhao T | Year | 2021 |
| Journal | J Neurosci Res | Volume | 99 |
| Issue | 10 | Pages | 2743-2758 |
| PubMed ID | 34133797 | Mgi Jnum | J:348046 |
| Mgi Id | MGI:7627270 | Doi | 10.1002/jnr.24905 |
| Citation | Zhao T, et al. (2021) Phenotypic differences in the inner ears of CBA/CaJ and C57BL/6J mice carrying missense and single base pair deletion mutations in the Cdh23 gene. J Neurosci Res 99(10):2743-2758 |
| abstractText | Different mutations in the cadherin 23 (CDH23) gene in different genetic backgrounds have been linked to either syndromic or nonsyndromic forms of deafness in humans. We previously reported a progressive hearing loss (HL) mouse model, the Cdh23(erl/erl) mouse, which carries a 208T > C mutation causing an amino acid substitution at S70P in C57BL/6J mice. To investigate the differences in Cdh23 mutation-related HL in different genetic backgrounds, we used the CRISPR/Cas9 system to generate homozygous mice in the CBA/CaJ background that have the same base pair missense mutation (208T > C) (Cdh23(erl2/erl2) ) as Cdh23(erl/erl) mice in the C57BL/6J background or a single base pair deletion (235G) (Cdh23(V2J2/V2J2) ) in the Cdh23 gene at exon 5. The two mutant mice exhibit hearing impairment across a broad range of frequencies. The progression of HL in Cdh23(erl2/erl2) mice is slower than that in Cdh23(erl/erl) mice. We also found structural abnormalities in the stereocilia of cochlear hair cells in Cdh23(erl2/erl2) and Cdh23(V2J2/V2J2) mice. Cdh23(V2J2/V2J2) mice show signs of vestibular dysfunction in open field behavior and swimming tests. In addition, we observed hair bundle defects in vestibular hair cells in Cdh23(V2J2/V2J2) mice. Our results suggest an interaction between the erl locus and the C57BL/6J background that exacerbates HL in Cdh23(erl/erl) mice. Moreover, our study confirms that the Cdh23 gene is essential for normal hearing and balance. These two novel mutant mouse strains provide excellent models for studying CDH23 mutation-related deafness in humans. |
