The Role of PMCA2 in Hearing Loss

描述（由申请人提供）：聋人（dfw）小鼠目前是隐性感音神经性耳聋的模型。然而，杂合子小鼠表现出不同的听力损失，这取决于背景和dfw等位基因的严重程度。致病突变影响编码质膜钙泵PMCA2的Atp2b2基因（Street等，1998）。本研究的最终目的是评估dfw杂合子作为年龄相关性听力损失（AHL）和噪声性听力损失（NIHL）的模型。将使用部分功能缺失等位基因（dfw）和功能缺失等位基因（dfw- j） （Penheiter等人，2001；Street等人，1998）。这两个等位基因都维持在CBA/CaJ背景下，这是小鼠听力的“黄金标准”。我们将使用听觉脑干反应（ABR）和失真积耳声发射（DPOAE）测量来测量听力损失。Corti的器官也将进行显微镜检查，以便将组织病理学与功能测量相关联。另一个目的是通过检测反杂合子对NIHL的易感性来研究dfw和waltzer (v)位点之间潜在的遗传相互作用。

DESCRIPTION (provided by applicant): The deafwaddler (dfw) mouse is presently a model for recessive sensorineural deafness. Heterozygous mice, however, show variable hearing loss depending on the background and the severity of the dfw allele. The causative mutation affects the Atp2b2 gene encoding the plasma membrane calcium pump PMCA2 (Street, et al., 1998). The ultimate goal of the present study is to evaluate dfw heterozygotes as a model for age-related hearing loss (AHL) and noise-induced hearing loss (NIHL). A partial loss-of-function allele (dfw) and a functional null allele (dfw-J) will be used (Penheiter et al., 2001; Street et al., 1998). Both alleles are maintained in a CBA/CaJ background, the "gold standard" for hearing in mice. We will measure hearing loss using auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements. The organ of Corti will also be examined microscopically in order to correlate histopathology with functional measurements. An additional aim is to investigate a potential genetic interaction between the dfw and waltzer (v) loci by examining the susceptibility to NIHL in trans-heterozygotes.