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小鼠年龄相关性听力损失的遗传学。III. 近交系和F1杂交系对噪声性听力损失的易感性。

Genetics of age-related hearing loss in mice. III. Susceptibility of inbred and F1 hybrid strains to noise-induced hearing loss.

作者信息

Erway L C, Shiau Y W, Davis R R, Krieg E F

机构信息

Department of Biological Sciences, University of Cincinnati, OH 45221,

出版信息

Hear Res. 1996 Apr;93(1-2):181-7. doi: 10.1016/0378-5955(95)00226-x.

Abstract

Some humans and mice are genetically predisposed to age-related hearing loss (AHL), and others are variously susceptible to noise-induced hearing loss (NIHL). The inbred C57BL/6J (B6) mice exhibit AHL at an early age, whereas the inbred CBA/CaJ (CB) mice do not. The B6 mice are much more susceptible to NIHL than are the CB mice (Shone et al., 1991; Li, 1992a). The B6 mice possess an Ahl gene which maps to chromosome 10 (Erway et al., 1995). This study was designed, using these two inbred strains plus two F1 hybrid strains of mice, to begin to test the hypothesis that the Ahl genotypes may influence the susceptibility to NIHL. These strains of mice (with putative genotypes) are: inbred CB (+/+) and B6 (Ahl/Ahl); hybrid CBB6F1 (+/Ahl) and B6D2F1 (Ahl/Ahl; D2 represents inbred DBA/2J). Twenty-four mice of each of these four strains were exposed to noise (110 dB for 0, 1 or 2 h) and tested for auditory-evoked brainstem response (ABR) thresholds. The CB and CBB6F1 strains of mice did not differ significantly from each other, exhibiting mostly temporary threshold shifts. The B6 and B6D2F1 strains of mice did not differ significantly from each other, but did exhibit permanent threshold shifts. These results support the hypothesis that genetic predisposition to AHL may be revealed at a younger age by NIHL. This suggests that it may be possible to use the NIHL to distinguish segregating genotypes (+/Ahl vs. Ahl/Ahl) among backcross progeny and thereby to identify and map single genes for AHL.

摘要

一些人类和小鼠在基因上易患年龄相关性听力损失(AHL),而另一些则对噪声性听力损失(NIHL)有不同程度的易感性。近交系C57BL/6J(B6)小鼠在幼年时就表现出AHL,而近交系CBA/CaJ(CB)小鼠则不会。B6小鼠比CB小鼠对NIHL更易感(Shone等人,1991年;Li,1992a)。B6小鼠拥有一个定位于10号染色体的Ahl基因(Erway等人,1995年)。本研究使用这两个近交系以及两个小鼠F1杂交系,旨在开始检验Ahl基因型可能影响对NIHL易感性的假说。这些小鼠品系(具有假定的基因型)为:近交系CB(+/+)和B6(Ahl/Ahl);杂交系CBB6F1(+/Ahl)和B6D2F1(Ahl/Ahl;D2代表近交系DBA/2J)。这四个品系的24只小鼠均暴露于噪声(110分贝,持续0、1或2小时),并测试听觉脑干反应(ABR)阈值。CB和CBB6F1品系的小鼠彼此之间无显著差异,大多表现为暂时性阈移。B6和B6D2F1品系的小鼠彼此之间无显著差异,但均表现出永久性阈移。这些结果支持了以下假说:NIHL可能在较年轻时揭示AHL的遗传易感性。这表明有可能利用NIHL来区分回交后代中的分离基因型(+/Ahl与Ahl/Ahl),从而识别和定位AHL的单个基因。

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