Abstract
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 (Slc44a2Δ/Δ) 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 Slc44a2Δ allele were backcrossed to the ARHL-resistant FVB/NJ strain and evaluated after backcross seven (N7) (99 % FVB). Slc44a2Δ/Δ mice produced abnormally spliced Slc44a2 transcripts that contain a frameshift and premature stop codons. Neither full-length SLC44A2 nor a putative truncated protein could be detected in Slc44a2Δ/Δ mice, suggesting a likely null allele. Auditory brain stem responses (ABRs) of mice carrying the Slc44a2Δ allele on an FVB/NJ genetic background were tested longitudinally between the ages of 2 and 10 months. By 6 months of age, Slc44a2Δ/Δ 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 +/Slc44a2Δ mice. After 6 months of age, Slc44a2Δ/Δ mutants exhibited progressive hearing loss at all frequencies and +/Slc44a2Δ mice exhibited moderate threshold elevations at high frequency. Histologic evaluation of Slc44a2Δ/Δ 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.
Highlights
SLC44A2 is a transmembrane glycoprotein (Nair et al 2004) that belongs to the solute carrier family of osmolyte transporters involved in transmembrane transport of small molecules (He et al 2009)
To reduce effects associated with age-related hearing loss (ARHL) in these strains, mice carrying the Slc44a2Δ allele were backcrossed to the ARHL-resistant FVB/NJ strain and evaluated after backcross seven
KHRI-3 showed strong reactivity with supporting cells, but not sensory cells, and the antibody target was called the Bsupporting cell antigen.^ We demonstrated upregulation of KHRI-3 antigen in areas of hair cell loss induced by drugs or noise (Ptok et al 1993)
Summary
SLC44A2 (solute carrier 44a2) is a transmembrane glycoprotein (Nair et al 2004) that belongs to the solute carrier family of osmolyte transporters involved in transmembrane transport of small molecules (He et al 2009). It is highly expressed in inner ear supporting cells and was discovered as the target of a monoclonal antibody, KHRI-3 (Zajic et al 1991). Since antibody to SLC44A2 adversely affects hair cell survival and hearing, we postulated that this protein must be essential for normal function of the inner ear. This study indicates a critical role of Slc44a2 in the maintenance of auditory function
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of the Association for Research in Otolaryngology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
