| First Author | Lu YC | Year | 2014 |
| Journal | PLoS One | Volume | 8 |
| Issue | 6 | Pages | e64906 |
| PubMed ID | 23755160 | Mgi Jnum | J:203206 |
| Mgi Id | MGI:5525188 | Doi | 10.1371/journal.pone.0064906 |
| Citation | Lu YC, et al. (2013) Differences in the pathogenicity of the p.H723R mutation of the common deafness-associated SLC26A4 gene in humans and mice. PLoS One 8(6):e64906 |
| abstractText | Mutations in the SLC26A4 gene are a common cause of human hereditary hearing impairment worldwide. Previous studies have demonstrated that different SLC26A4 mutations have different pathogenetic mechanisms. By using a genotype-driven approach, we established a knock-in mouse model (i.e., Slc26a4(tm2Dontuh/tm2Dontuh) mice) homozygous for the common p.H723R mutation in the East Asian population. To verify the pathogenicity of the p.H723R allele in mice, we further generated mice with compound heterozygous mutations (i.e., Slc26a4(tm1Dontuh/tm2Dontuh) ) by intercrossing Slc26a4(+/tm2Dontuh) mice with Slc26a4(tm1Dontuh/tm1Dontuh) mice, which segregated the c.919-2A>G mutation with an abolished Slc26a4 function. Mice were then subjected to audiologic assessments, a battery of vestibular evaluations, inner ear morphological studies, and noise exposure experiments. The results were unexpected; both Slc26a4(tm2Dontuh/tm2Dontuh) and Slc26a4(tm1Dontuh/tm2Dontuh) mice showed normal audiovestibular phenotypes and inner ear morphology, and they did not show significantly higher shifts in hearing thresholds after noise exposure than the wild-type mice. The results indicated not only the p.H723R allele was non-pathogenic in mice, but also a single p.H723R allele was sufficient to maintain normal inner ear physiology in heterozygous compound mice. There might be discrepancies in the pathogenicity of specific SLC26A4 mutations in humans and mice; therefore, precautions should be taken when extrapolating the results of animal studies to humans. |
