Quantitative trait loci on chromosome 5 for susceptibility to frequency-specific effects on hearing in DBA/2J mice.
Quantitative trait loci on chromosome 5 for susceptibility to frequency-specific effects on hearing in DBA/2J mice.
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DOI：
10.1538/expanim.14-0110
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发表时间：
2015
影响因子：
2.4
通讯作者：
Kikkawa Y
中科院分区：
文献类型：
--
作者：
Suzuki S;Ishikawa M;Ueda T;Ohshiba Y;Miyasaka Y;Okumura K;Yokohama M;Taya C;Matsuoka K;Kikkawa Y
如本研究证实，DBA/2J品系是人类早发性进行性听力损失的一个模型。DBA/2J小鼠表现出从超声频率声音到低频声音的听力损失进展，并且在7个月龄之前在所有频率下都有严重的听力损失。已知DBA/2J小鼠的早发性听力损失分别是由钙黏蛋白23基因的ahl（Cdh23ahl）等位基因和肌动蛋白集束蛋白2基因的ahl8（Fscn2ahl8）等位基因的影响所致。尽管在8千赫和16千赫刺激下的听力损失中检测到Fscn2ahl8等位基因有很强的作用，在8千赫时的优势对数计分（LOD score）为5.02，在16千赫时为8.84，但对于5号染色体上分别位于50.3 - 54.5、64.6 - 119.9和119.9 - 137.0兆碱基区间的三个新的数量性状基因座（QTLs）也证明了其对听力损失的影响，通过使用（DBA/2J×C57BL/6J）F1×DBA/2J回交小鼠进行数量性状基因座连锁作图，在16千赫特定高频听力损失的显著优势对数计分（LOD score）为2.80 - 3.91。此外，我们表明Fscn2ahl8对32千赫刺激下的早发性听力损失的作用极低，并提出了Cdh23ahl等位基因以及在该超声频率下另一个导致听力损失的显性数量性状基因座（位点）产生影响的可能性。因此，我们的结果表明特定频率的数量性状基因座控制着DBA/2J小鼠的早发性听力损失。
The DBA/2J strain is a model for early-onset, progressive hearing loss in humans, as confirmed in the present study. DBA/2J mice showed progression of hearing loss to low-frequency sounds from ultrasonic-frequency sounds and profound hearing loss at all frequencies before 7 months of age. It is known that the early-onset hearing loss of DBA/2J mice is caused by affects in the ahl (Cdh23ahl) and ahl8 (Fscn2ahl8) alleles of the cadherin 23 and fascin 2 genes, respectively. Although the strong contributions of the Fscn2ahl8 allele were detected in hearing loss at 8- and 16-kHz stimuli with LOD scores of 5.02 at 8 kHz and 8.84 at 16 kHz, hearing loss effects were also demonstrated for three new quantitative trait loci (QTLs) for the intervals of 50.3–54.5, 64.6–119.9, and 119.9–137.0 Mb, respectively, on chromosome 5, with significant LOD scores of 2.80–3.91 for specific high-frequency hearing loss at 16 kHz by quantitative trait loci linkage mapping using a (DBA/2J × C57BL/6J) F1 × DBA/2J backcross mice. Moreover, we showed that the contribution of Fscn2ahl8 to early-onset hearing loss with 32-kHz stimuli is extremely low and raised the possibility of effects from the Cdh23ahl allele and another dominant quantitative trait locus (loci) for hearing loss at this ultrasonic frequency. Therefore, our results suggested that frequency-specific QTLs control early-onset hearing loss in DBA/2J mice.