mdfw: A deafness susceptibility locus that interacts with deaf waddler (dfw)
mdfw: A deafness susceptibility locus that interacts with deaf waddler (dfw)
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DOI：
10.1006/geno.1997.4869
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发表时间：
1997-09-15
期刊：
影响因子：
4.4
通讯作者：
Nishina, PM
中科院分区：
文献类型：
--
作者：
NobenTrauth, K;Zheng, QY;Nishina, PM
聋蹒跚（dfw）突变是研究小鼠神经上皮听力缺陷生物学的模型系统。在这里，我们描述了一个新的等位基因聋waddler（dfw（2 J））的鉴定和表征，并提出证据的听力易感性位点（mdfw）与dfw相互作用。我们发现CBy-dfw（2 J）/dfw（2 J）纯合子对高达100 dB的声压级刺激没有可辨别的听性脑干反应（ABR），表明深度耳聋。有趣的是，ABR iu CBy-dfw（2 J）/+杂合子也是异常的，表现出进行性听力损失特征的年龄依赖性阈值升高。当与CAST/Ei株异交时，只有24%的F2 CBy/CAST-dfw（2 J）/+杂合子表现出ABR阈值升高，这表明在dfw（2 J）/+杂合子中控制堆积功能的第二个基因座，在CBy/CAST-dfw（2 J）互交中分离。通过连锁分析，我们将该位点（mdfw）定位于第10号染色体，标记D10 Mit 127和之间。D10 Mit 185，在4.0 +/- 1.1 cM的遗传区间内。所有发生听力损失的CBy/CAST-dfw（2 J）/+杂合子都是CBy衍生的隐性等位基因（mdfw（c））的纯合子。相比之下，表达甚至单个拷贝的CAST/Ei衍生的mdfw等位基因（Mdfw）的CBy/CAST-dfw（2 J）/+杂合子保留其正常的堆积功能。我们的研究结果揭示了mdfw和dfw基因之间的上位关系，并提供了一个模型系统，以研究非综合征性听力损失的小鼠。(C)北京：科学出版社.
The deaf waddler (dfw) mutation is a model system to study the biology of neuroepithelial hearing defects in mice. Here we describe the identification and characterization of a new allele of deaf waddler (dfw(2J)) and present evidence for a hearing susceptibility locus (mdfw) that interacts with dfw. We found that CBy-dfw(2J)/dfw(2J) homozygotes exhibit no discernible auditory brainstem responses (ABR) to sound pressure level stimuli up to 100 dB, indicating a profound deafness. Interestingly, the ABR iu CBy-dfw(2J)/+ heterozygotes is also abnormal, showing age-dependent elevated thresholds characteristic of a progressive hearing loss, When outcrossed onto the CAST/Ei strain, only 24% of the F2 CBy/CAST-dfw(2J)/+ heterozygotes displayed increased ABR thresholds, suggesting that a second locus, controlling heaping function in dfw(2J)/+ heterozygotes, was segregating in the CBy/CAST-dfw(2J) intercross. By linkage analysis, we localized this locus (mdfw) to Chromosome 10, between markers D10Mit127 and. D10Mit185, within a 4.0 +/- 1.1 cM genetic interval. All CBy/CAST-dfw(2J)/+ heterozygotes that develop hearing loss are homozygous for the CBy-derived recessive allele (mdfw(c)). In contrast, CBy/CAST-dfw(2J)/+ heterozygotes expressing even a single copy of the CAST/Ei-derived mdfw allele (Mdfw) retain their normal heaping function. Our results reveal an epistatic relationship between the mdfw and the dfw genes and provide a model system to study nonsyndromic hearing loss in mice. (C) 1997 Academic Press.