| First Author | Kommareddi P | Year | 2015 |
| Journal | J Assoc Res Otolaryngol | Volume | 16 |
| Issue | 6 | Pages | 695-712 |
| PubMed ID | 26463873 | Mgi Jnum | J:239440 |
| Mgi Id | MGI:5828923 | Doi | 10.1007/s10162-015-0547-3 |
| Citation | Kommareddi P, et al. (2015) Hair Cell Loss, Spiral Ganglion Degeneration, and Progressive Sensorineural Hearing Loss in Mice with Targeted Deletion of Slc44a2/Ctl2. J Assoc Res Otolaryngol 16(6):695-712 |
| abstractText | SLC44A2 (solute carrier 44a2), also known as CTL2 (choline transporter-like protein 2), is expressed in many supporting cell types in the cochlea and is implicated in hair cell survival and antibody-induced hearing loss. In mice with the mixed C57BL/6-129 background, homozygous deletion of Slc44a2 exons 3-10 (Slc44a2(Delta/Delta)resulted in high-frequency hearing loss and hair cell death. To reduce effects associated with age-related hearing loss (ARHL) in these strains, mice carrying the Slc44a2Delta allele were backcrossed to the ARHL-resistant FVB/NJ strain and evaluated after backcross seven(N7) (99 % FVB). Slc44a2(Delta/Delta) mice produced abnormally spliced Slc44a2 transcripts that contain a frame shift and premature stop codons. Neither full-length SLC44A2 nor a putative truncated protein could be detected in Slc44a2(Delta/Delta) mice, suggesting a likely null allele. Auditory brain stem responses (ABRs) of mice carrying the Slc44a2Delta allele on an FVB/NJ genetic background were tested longitudinally between the ages of 2 and 10 months. By 6 months of age,Slc44a2(Delta/Delta) mice exhibited hearing loss at 32 kHz,but at 12 and 24 kHz had sound thresholds similar to those of wild-type Slc44a2(+/+) and heterozygous +/Slc44a2Delta mice. After 6 months of age, Slc44a2(Delta/Delta) mutants exhibited progressive hearing loss at all frequencies and +/Slc44a2(Delta) mice exhibited moderate threshold elevations at high frequency. Histologic evaluation of Slc44a2(Delta/Delta) mice revealed extensive hair cell and spiral ganglion cell loss, especially in the basal turn of the cochlea. We conclude that Slc44a2 function is required for long-term hair cell survival and maintenance of hearing. |
