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We used homologous recombination in C57BL\/6\u2009NJ (B6N) and 129S1\/SvImJ (129S1) embryonic stem cells to engineer mouse strains with reciprocal single base pair substitutions (B6-\n Cdh23<\/jats:italic>\n \n c.753A<\/jats:italic>\n >\n G<\/jats:italic>\n <\/jats:sup>\n and 129S1-\n Cdh23<\/jats:italic>\n \n c.753G<\/jats:italic>\n >\n A<\/jats:italic>\n <\/jats:sup>\n ). We compared ABR thresholds and cochlear pathologies of these SNV mice with those of congenic (B6.129S1-\n Cdh23<\/jats:italic>\n \n Ahl<\/jats:italic>\n +\n <\/jats:sup>\n and 129S1.B6-\n Cdh23<\/jats:italic>\n \n ahl<\/jats:italic>\n <\/jats:sup>\n ) and parental (B6N and 129S1) strain mice. Results verified the protective effect of the\n Cdh23<\/jats:italic>\n \n c.753G<\/jats:italic>\n <\/jats:sup>\n allele, which prevented high frequency hearing loss in B6 mice to at least 18 months of age, and the AHL-inducing effect of the\n Cdh23<\/jats:italic>\n \n c.753A<\/jats:italic>\n <\/jats:sup>\n allele, which worsened hearing loss in 129S1 mice. ABR thresholds differed between 129S-\n Cdh23<\/jats:italic>\n \n c.753A<\/jats:italic>\n <\/jats:sup>\n SNV and 129S1.B6-\n Cdh23<\/jats:italic>\n \n ahl<\/jats:italic>\n <\/jats:sup>\n congenic mice, and a linkage backcross involving these strains localized a Chr 10 QTL contributing to the difference. These results illustrate the large effects that strain background and congenic regions have on the hearing loss associated with\n Cdh23<\/jats:italic>\n \n c.753<\/jats:italic>\n <\/jats:sup>\n alleles. Importantly, the B6-\n Cdh23<\/jats:italic>\n \n c.753G<\/jats:italic>\n <\/jats:sup>\n strain can be used to eliminate the confounding influence of the\n Cdh23<\/jats:italic>\n \n c.753A<\/jats:italic>\n <\/jats:sup>\n variant in hearing studies of B6 mice and mutant mice on the B6 background.\n <\/jats:p>","DOI":"10.1038\/srep44450","type":"journal-article","created":{"date-parts":[[2017,3,13]],"date-time":"2017-03-13T09:44:33Z","timestamp":1489398273000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Effects of Cdh23 single nucleotide substitutions on age-related hearing loss in C57BL\/6 and 129S1\/Sv mice and comparisons with congenic strains"],"prefix":"10.1038","volume":"7","author":[{"given":"Kenneth R.","family":"Johnson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leona H.","family":"Gagnon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalian","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Salvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,13]]},"reference":[{"key":"BFsrep44450_CR1","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1146\/annurev-publhealth-032013-182510","volume":"35","author":"KE Bainbridge","year":"2014","unstructured":"Bainbridge, K. 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