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 Cdh23erl/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) (Cdh23erl2/erl2 ) as Cdh23erl/erl mice in the C57BL/6J background or a single base pair deletion (235G) (Cdh23V2J2/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 Cdh23erl2/erl2 mice is slower than that in Cdh23erl/erl mice. We also found structural abnormalities in the stereocilia of cochlear hair cells in Cdh23erl2/erl2 and Cdh23V2J2/V2J2 mice. Cdh23V2J2/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 Cdh23V2J2/V2J2 mice. Our results suggest an interaction between the erl locus and the C57BL/6J background that exacerbates HL in Cdh23erl/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.
Keywords: Cdh23; RRID:AB_10015251; RRID:AB_10681108; RRID:AB_10700003; RRID:AB_2534079; RRID:AB_955447; RRID:Addgene_42230; RRID:IMSR_JAX:000654; RRID:IMSR_JAX:000664; RRID:MGI:6501722; RRID:MGI:6501724; RRID:SCR_002798; genetic background; hearing loss; mouse model; vestibular dysfunction.
© 2021 Wiley Periodicals LLC.