Exome sequencing identifies a missense mutation in Isl1 associated with low penetrance otitis media in dearisch mice.
Exome sequencing identifies a missense mutation in Isl1 associated with low penetrance otitis media in dearisch mice.
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DOI：
10.1186/gb-2011-12-9-r90
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发表时间：
2011-09-21
期刊：
影响因子：
12.3
通讯作者：
Steel KP
中科院分区：
文献类型：
--
作者：
Hilton JM;Lewis MA;Grati M;Ingham N;Pearson S;Laskowski RA;Adams DJ;Steel KP
中耳炎（中耳炎）非常常见，如果不解决，可能导致严重的并发症。遗传学研究表明，遗传成分，但很少有基因，有助于这种情况是已知的。小鼠突变体对鉴定诱发中耳炎的基因做出了重大贡献。去毛小鼠突变体是一种ENU诱导的突变体，通过其受损的Preyer反射（响应声音的耳轻弹）检测。听觉脑干反应显示，早在三周大的时候阈值就升高了。系谱分析提示显性部分外显遗传。脱髓鞘突变者的中耳表现为粘膜增厚和细胞渗出，提示慢性中耳炎伴渗出，合并急性感染。包括感觉毛细胞在内的内耳看起来正常。由于表型的低突变率，不可能进行正常的突变回交作图。因此，外显子组测序，以确定一个非保守的酪氨酸半胱氨酸（Y 71 C）的错义突变的Isl 1基因，Isl 1Drsh。Isl 1在正常中耳粘膜中表达。研究结果表明Isl 1Drsh突变可能使携带者易患中耳炎。Dearisch，Isl 1Drsh，代表了小鼠Isl 1基因中的第一个点突变，并表明该基因以前未被认识到的作用。这也是第一个记录的外显子组测序的C3 HeB/FeJ背景相关的许多ENU诱导的突变体。最重要的是，外显子组重测序的权力，以确定ENU诱导的突变没有映射的基因位点进行了说明。
Inflammation of the middle ear (otitis media) is very common and can lead to serious complications if not resolved. Genetic studies suggest an inherited component, but few of the genes that contribute to this condition are known. Mouse mutants have contributed significantly to the identification of genes predisposing to otitis media The dearisch mouse mutant is an ENU-induced mutant detected by its impaired Preyer reflex (ear flick in response to sound). Auditory brainstem responses revealed raised thresholds from as early as three weeks old. Pedigree analysis suggested a dominant but partially penetrant mode of inheritance. The middle ear of dearisch mutants shows a thickened mucosa and cellular effusion suggesting chronic otitis media with effusion with superimposed acute infection. The inner ear, including the sensory hair cells, appears normal. Due to the low penetrance of the phenotype, normal backcross mapping of the mutation was not possible. Exome sequencing was therefore employed to identify a non-conservative tyrosine to cysteine (Y71C) missense mutation in the Islet1 gene, Isl1Drsh. Isl1 is expressed in the normal middle ear mucosa. The findings suggest the Isl1Drshmutation is likely to predispose carriers to otitis media. Dearisch, Isl1Drsh, represents the first point mutation in the mouse Isl1 gene and suggests a previously unrecognized role for this gene. It is also the first recorded exome sequencing of the C3HeB/FeJ background relevant to many ENU-induced mutants. Most importantly, the power of exome resequencing to identify ENU-induced mutations without a mapped gene locus is illustrated.
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唐氏综合症小鼠模型中的中耳炎。
DOI：
10.1111/j.1365-2613.2009.00677.x
发表时间：
2009-10
影响因子：
3
作者：
Han F;Yu H;Zhang J;Tian C;Schmidt C;Nava C;Davisson MT;Zheng QY
通讯作者：
Zheng QY
影响因子：
1.7
作者：
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通讯作者：
Yalcin, Sinasi
影响因子：
14.9
作者：
Finn RD;Mistry J;Tate J;Coggill P;Heger A;Pollington JE;Gavin OL;Gunasekaran P;Ceric G;Forslund K;Holm L;Sonnhammer EL;Eddy SR;Bateman A
通讯作者：
Bateman A
影响因子：
4.4
作者：
Greenhill, Claire J.;Rose-John, Stefan;Jenkins, Brendan J.
通讯作者：
Jenkins, Brendan J.
影响因子：
120.7
作者：
Casselbrant, ML;Mandel, EM;Ferrell, RE
通讯作者：
Ferrell, RE