Alleles that modulate late life hearing in genetically heterogeneous mice

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• 作者：Jochen Schacht^a ; Richard Altschuler^a ; David T. Burke^b ; Shu Chen^c ; David Dolan^a ; Andrzej T. Galecki^c ; ^d ; ^e ; David Kohrman^a ; ^b ; Richard A. Miller^d ; ^f ; ^g ; ^{millerr@umich.edu}
• 关键词：Aging ; Presbycusis ; Gene mapping ; Cochlea ; Mice ; Animal models
• 刊名：Neurobiology of Aging
• 出版年：2012
• 期刊代码：202_01974580
• 类别：med
• 出版时间：August, 2012
• 卷：33
• 期：8
• 页码：1842.e15-1842.e29
• 文件大小：2239 K

摘要

A genetically heterogeneous population of mice was tested for hearing at 8, 18, and 22 months by auditory brainstem response (ABR), and genotyped at 128 markers to identify loci that modulate late life hearing loss. Half of the test mice were exposed to noise for 2 hours at age 20 months. Polymorphisms affecting hearing at 18 months were noted on chromosomes 2, 3, 7, 10, and 15. Most of these loci had effects only on responses to 48 kHz stimuli, but a subset also influenced the auditory brainstem response at lower frequencies. Loci on chromosomes 4, 10, 12, and 14 had significant effects on hearing at 22 months in noise-exposed mice, and loci on chromosomes 10 and 11 had effects on mice not exposed to noise. Outer hair cell loss was modulated by polymorphisms on chromosomes 10, 11, 12, 17, and 19. Resistance to age-related hearing loss is thus modulated by a set of genetic effects, some age-specific, some frequency specific, some dependent on prior exposure to noise, and some of which compromise survival of cochlear hair cells.