Age-related hearing loss and the ahl locus in mice

Age-related hearing loss and the ahl locus in mice
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DOI:
10.1016/s0378-5955(03)00365-4
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发表时间:
2004-02-01
期刊:
影响因子:
2.8
通讯作者:
Johnson, KR
Johnson, KR
中科院分区:
医学1区
文献类型:
--
作者:
Keithley, EM;Canto, C;Johnson, KR

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C5713L/6(136)小鼠在中年左右开始出现听力损失和耳蜗变性,而CAST/EI(CAST)小鼠直到老年都保持正常听力。由B6((AHL)/(AHL))和CAST(+(AHL)/+(AHL))小鼠杂交产生的纯合子同源品系(B6.CAST-+(AHL))与136只小鼠具有相同的基因组物质,但AHL基因座的区域来自CAST。在这项研究中,我们确定了同源品系中10号染色体铸型衍生区域的范围,并检查了所有三个品系的小鼠在9至25个月龄时的听力损失和耳蜗形态。B6小鼠的结果与之前描述的结果相似。CAST小鼠即使在24个月大的时候也没有表现出明显的听力损失;然而,他们。有少量的神经节细胞变性。B6.CAST-+(AHL)小鼠对早发性听力损失和基底转角变性具有保护作用。但年长的动物确实表现出一些听力损失和神经节细胞退化。我们的结论是,除AHL外,基因座也是B6和CAST小鼠听力损失差异的原因。这些结果说明了与年龄相关的小鼠听力损失的复杂遗传,并可能对人类老年性耳聋的研究有所启示。(C)2003爱思唯尔B.V.保留所有权利。
C5713L/6 (136) mice experience hearing loss and cochlear degeneration beginning about mid-life, whereas CAST/Ei (CAST) mice retain normal hearing until old age. A locus contributing to the hearing loss of B6 mice, named age-related hearing loss (ahl), was mapped to Chromosome 10. A homozygous, congenic strain of mice (B6.CAST-+(ahl)), generated by crossing B6 ((ahl)/(ahl)) and CAST (+(ahl)/+(ahl)) mice has the same genomic material as the 136 mice except in the region of the ahl locus, which is derived from CAST. In this study, we have determined the extent of the CAST-derived region of Chromosome 10 in the congenic strain and have examined mice of all three strains for hearing loss and cochlear morphology between 9 and 25 months of age. Results for B6 mice were similar to those described previously. CAST mice showed no detectable hearing loss even at 24 months of age; however, they. had a small amount of ganglion cell degeneration. B6.CAST-+(ahl) mice were protected from early onset hearing loss and basal turn degeneration. but older animals did show some hearing loss and ganglion cell degeneration. We conclude that loci in addition to ahl contribute to the differences in hearing loss between B6 and CAST mice. These results illustrate the complex inheritance of age-related hearing loss in mice and may have implications for the study of human presbycusis. (C) 2003 Elsevier B.V. All rights reserved.