Ahl2, a second locus affecting age-related hearing loss in mice
Ahl2, a second locus affecting age-related hearing loss in mice
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DOI：
10.1006/geno.2002.6858
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发表时间：
2002-11-01
期刊：
影响因子：
4.4
通讯作者：
Zheng, QY
中科院分区：
文献类型：
--
作者：
Johnson, KR;Zheng, QY
具有年龄相关性听力损失（阿勒）的近交系小鼠为研究人类老年性耳聋的遗传基础提供了有价值的模型。在这里，我们报告了小鼠第二个阿勒基因座（命名为Ahl 2）的遗传图谱，该基因座是NOD/LtJ和C57 BL/6 J小鼠之间听力损失发作时间8至10个月差异的主要原因。对来自（C57 BL/6 J X NOD/LtJ）X NOD/LtJ回交的110个后代的全基因组连锁扫描显示ABR阈值与5号染色体上的标记具有统计学显著性关联，D5 Mit 309的峰值lod得分为5.5。在6个月大时，在该基因座（基因型ahl 2/ahl 2）遗传了两个拷贝的隐性NOD/LtJ衍生等位基因的回交后代表现出平均比杂合子小鼠高26分贝的ABR阈值。对（CAST/Ei × NOD/LtJ）× NOD/LtJ回交的分析表明，可归因于Ahl 2的听力损失依赖于易感的阿勒基因型，所述回交分离了10号染色体上Ahl 2和阿勒基因座上的菌株特异性等位基因。在与N 0 D/LtJ的杂交中观察到的Ahl 2的统计学显著作用在涉及具有早发性阿勒的三种其他菌株：A/J、BUB/BnJ和SKH 2/J的杂交中未观察到。
inbred mouse strains with age-related hearing loss (AHL) provide valuable models for studying the genetic basis of human presbycusis. Here we report the genetic mapping of a second AHL locus in mice (designated Ahl2) that is a major contributor to the 8- to 10-month difference in hearing loss onset times between NOD/LtJ and C57BL/6J mice. A whole-genome linkage scan of 110 progeny from a (C57BL/6J X NOD/LtJ) X NOD/LtJ backcross revealed statistically significant associations of ABR thresholds with markers on chromosome 5, with a peak lod score of 5.5 for D5Mit309. At 6 months of age, backcross progeny that inherited two copies of the recessive NOD/LtJ-derived allele at this locus (genotype ahl2/ahl2) exhibited ABR thresholds that were on average 26 decibels above those of heterozygous mice. Analysis of a (CAST/Ei x NOD/LtJ) x NOD/LtJ backcross, which segregates strain-specific alleles at both Ahl2 and the Ahl locus on chromosome 10, showed that the hearing loss attributable to Ahl2 is dependent on a predisposing Ahl genotype. The statistically significant effect of Ahl2 observed in crosses with NOD/LtJ was not seen in crosses involving three other strains with early onset AHL: A/J, BUB/BnJ, and SKH2/J.