A major gene affecting age-related hearing loss is common to at least ten inbred strains of mice
A major gene affecting age-related hearing loss is common to at least ten inbred strains of mice
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DOI：
10.1006/geno.2000.6377
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发表时间：
2000-12-01
期刊：
影响因子：
4.4
通讯作者：
Erway, LC
中科院分区：
文献类型：
--
作者：
Johnson, KR;Zheng, QY;Erway, LC
近交系小鼠为了解人类老年性耳聋或年龄相关性听力损失（阿勒）的遗传基础提供了有希望的模型。在这里，我们表明，相同的染色体10基因（阿勒）是一个主要贡献者AHL在其他九个近交系小鼠品系-129 P1/ReJ，A/J，BALB/cByJ，BUB/BnJ，C57 BR/cdJ，DBA/2 J，NOD/LtJ，SKH 2/J，和STOCK 760。这些近交系与听力正常的近交系CAST/Ei之间的F1杂种保留了良好的听力，表明阿勒的遗传是隐性的。为了遵循听力损失的分离，将F1杂种与具有阿勒的亲本株系回交。听觉诱发的脑干反应阈值被用来评估听力超过1500 N2小鼠和分析的数量性状与染色体10标记的连锁关系。在9个品系的回交中均发现了高度显著的连锁，其中在标记DIOMit 112附近的可能性最高（LOD > 70）。阿勒的图谱位置靠近waltzer突变（v）和聋waddler基因座修饰基因（mdfw），表明可能存在等位性。C57 BL/6 J和NOD/LtJ小鼠的杂交结果表明，这两个品系之间AHL发作的6- 10个月差异不是由于阿勒基因的等位基因异质性。(C)北京大学出版社.
Inbred strains of mice offer promising models for understanding the genetic basis of human presbycusis or age-related hearing loss (AHL), We previously mapped a major gene affecting AHL in C57BL/6J mice. Here, we show that the same Chromosome 10 gene (Ahl) is a major contributor to AHL in nine other inbred mouse strains-129P1/ReJ, A/J, BALB/cByJ, BUB/BnJ, C57BR/cdJ, DBA/2J, NOD/LtJ, SKH2/J, and STOCK760. F1 hybrids between each of these inbred strains and the normal-hearing inbred strain CAST/Ei retain good hearing, indicating that inheritance of AHL is recessive. To follow segregation of hearing loss, F1 hybrids were backcrossed to the parental strains with AHL. Auditory-evoked brain-stem response thresholds were used to assess hearing in more than 1500 N2 mice and analyzed as quantitative traits for linkage associations with Chromosome 10 markers. Highly significant linkage was found in all nine strain backcrosses, with the highest probability (LOD > 70) near the marker DIOMit112 This map position for Ahl is near the waltzer mutation (v) and the modifier of deaf waddler locus (mdfw), suggesting the possibility of allelism. Results from an intercross of C57BL/6J and NOD/LtJ mice indicate that the 6- to 10-month difference in AHL onset between these two strains is not due to allelic heterogeneity of the Ahl gene. (C) 2000 Academic Press.