title: Hair Cell Loss, Spiral Ganglion Degeneration, and Progressive  Sensorineural Hearing Loss in Mice with Targeted Deletion  of Slc44a2/Ctl2.
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 (Slc44a2(Δ/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). Slc44a2(Δ/Δ) 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(Δ/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,Slc44a2(Δ/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, Slc44a2(Δ/Δ) mutants exhibited progressive hearing loss at all frequencies and +/Slc44a2(Δ) mice exhibited moderate threshold elevations at high frequency. Histologic evaluation of Slc44a2(Δ/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.
authors.forename: Pavan
authors.initials: P
authors.lastname: Kommareddi
authors.forename: Thankam
authors.initials: T
authors.lastname: Nair
authors.forename: Bala Naveen
authors.initials: BN
authors.lastname: Kakaraparthi
authors.forename: Maria M
authors.initials: MM
authors.lastname: Galano
authors.forename: Danielle
authors.initials: D
authors.lastname: Miller
authors.forename: Irina
authors.initials: I
authors.lastname: Laczkovich
authors.forename: Trey
authors.initials: T
authors.lastname: Thomas
authors.forename: Lillian
authors.initials: L
authors.lastname: Lu
authors.forename: Kelli
authors.initials: K
authors.lastname: Rule
authors.forename: Lisa
authors.initials: L
authors.lastname: Kabara
authors.forename: Ariane
authors.initials: A
authors.lastname: Kanicki
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Hughes
authors.forename: Julie M
authors.initials: JM
authors.lastname: Jones
authors.forename: Mark
authors.initials: M
authors.lastname: Hoenerhoff
authors.forename: Susan G
authors.initials: SG
authors.lastname: Fisher
authors.forename: Richard A
authors.initials: RA
authors.lastname: Altschuler
authors.forename: David
authors.initials: D
authors.lastname: Dolan
authors.forename: David C
authors.initials: DC
authors.lastname: Kohrman
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Saunders
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D017353:Gene Deletion; D006198:Hair Cells, Auditory / Q000473:pathology*; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D013136:Spiral Ganglion / Q000473:pathology*
chemical_list: D026901:Membrane Transport Proteins; C571060:SLC44A2 protein, mouse