| First Author | McCullough BJ | Year | 2004 |
| Journal | Hear Res | Volume | 195 |
| Issue | 1-2 | Pages | 90-102 |
| PubMed ID | 15350283 | Mgi Jnum | J:92390 |
| Mgi Id | MGI:3052571 | Doi | 10.1016/j.heares.2004.05.003 |
| Citation | McCullough BJ, et al. (2004) Haplo-insufficiency revealed in deafwaddler mice when tested for hearing loss and ataxia. Hear Res 195(1-2):90-102 |
| abstractText | The auditory and vestibular systems rely on the plasma membrane calcium ATPase, isoform 2 (PMCA2) to extrude calcium that enters the stereocilia during transduction. Mutations in the gene encoding this protein result in recessive sensorineural deafness and ataxia in the deafwaddler mouse. In this study, we report the identification of a new allele of deafwaddler, [Formula: see text]. This allele contains a 4-nucleotide deletion resulting in a frame-shift and predicted truncation of PMCA2. No protein is detected in [Formula: see text] homozygotes. To examine the dependence of auditory and vestibular function on PMCA2 activity, we compared [Formula: see text] with another functional null allele, [Formula: see text], and the partial loss-of-function allele, dfw. All mice studied were in the good-hearing CBA/CaJ background. Heterozygotes of either functional null allele displayed highly significant hearing loss by auditory-evoked brainstem responses relative to controls [Formula: see text], particularly at high frequencies ( [Formula: see text] 24 kHz). Ataxia was also apparent in these mice on an accelerating rotarod [Formula: see text]. In contrast, +/dfw mice were not measurably different from controls in either behavioral test. dfw/dfw mice were deaf, but showed less ataxia than [Formula: see text] or [Formula: see text] mice. These results demonstrate that hearing loss and ataxia are dependent on gene dosage and PMCA2 dysfunction. |
