英國(guó)科學(xué)家最近發(fā)表在《美國(guó)國(guó)家科學(xué)院院刊》上的一份研究報(bào)告稱,，小核糖核酸miR-96發(fā)生變異，可導(dǎo)致漸進(jìn)性失聰,。該分子機(jī)制的發(fā)現(xiàn)為改善聽力損失和失聰?shù)闹委熓侄蔚於嘶A(chǔ)。
該研究由英國(guó)謝菲爾德大學(xué)和劍橋桑格研究院等幾所研究機(jī)構(gòu)科學(xué)家共同完成,。通過對(duì)小白鼠的研究，研究人員發(fā)現(xiàn),，miR-96與哺乳動(dòng)物耳蝸發(fā)育密切相關(guān)，miR-96突變會(huì)導(dǎo)致人和小鼠漸進(jìn)性失聰,。
研究表明,，通常miR-96會(huì)在特定階段影響許多與發(fā)育相關(guān)的不同基因表達(dá)，進(jìn)而調(diào)節(jié)毛細(xì)胞的生長(zhǎng)過程。一旦小鼠體內(nèi)miR-96基因中某一區(qū)域的單個(gè)堿基對(duì)突變,，就會(huì)導(dǎo)致小鼠眾多的基因表達(dá)的改變,。研究論文指出，miR-96發(fā)生突變,，使得小鼠在出生后,，其內(nèi)耳和外耳毛細(xì)胞出現(xiàn)生物物理變異之前，感覺毛細(xì)胞的生理發(fā)育即已受到影響,。此外,，miR-96突變后，毛細(xì)胞靜纖毛束的發(fā)育和耳蝸內(nèi)聽覺神經(jīng)聯(lián)系的構(gòu)建都會(huì)受到影響,，這不僅會(huì)影響毛細(xì)胞的敏銳程度，還會(huì)影響感覺神經(jīng)的電信號(hào)傳遞,。據(jù)此,，研究人員認(rèn)為，miR-96會(huì)調(diào)節(jié)耳蝸毛細(xì)胞生理發(fā)育進(jìn)程,，也會(huì)影響耳蝸毛細(xì)胞的形態(tài),，對(duì)哺乳動(dòng)物的聽覺系統(tǒng)至關(guān)重要。
該項(xiàng)目的領(lǐng)導(dǎo)者,、謝菲爾德大學(xué)沃爾特·馬科蒂博士指出,，有很多人包括一些新生兒和小孩會(huì)受到漸進(jìn)性失聰?shù)挠绊懀茖W(xué)家對(duì)于漸進(jìn)性失聰?shù)倪z傳因素了解甚少,。新發(fā)現(xiàn)在增進(jìn)科學(xué)家對(duì)此了解的同時(shí),，也為未來該疾病的治療提供了新的分子標(biāo)靶,。（生物谷Bioon.com）
生物谷推薦原文出處：
PNAS doi: 10.1073/pnas.1016646108
miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells
Stephanie Kuhna,1, Stuart L. Johnsona,1, David N. Furnessb, Jing Chenc, Neil Inghamc, Jennifer M. Hiltonc, Georg Steffesc, Morag A. Lewisc, Valeria Zampinia,d, Carole M. Hackneya, Sergio Masettod, Matthew C. Holleya, Karen P. Steelc, and Walter Marcottia,2
Abstract
MicroRNAs (miRNAs) are small noncoding RNAs able to regulate a broad range of protein-coding genes involved in many biological processes. miR-96 is a sensory organ-specific miRNA expressed in the mammalian cochlea during development. Mutations in miR-96 cause nonsyndromic progressive hearing loss in humans and mice. The mouse mutant diminuendo has a single base change in the seed region of the Mir96 gene leading to widespread changes in the expression of many genes. We have used this mutant to explore the role of miR-96 in the maturation of the auditory organ. We found that the physiological development of mutant sensory hair cells is arrested at around the day of birth, before their biophysical differentiation into inner and outer hair cells. Moreover, maturation of the hair cell stereocilia bundle and remodelling of auditory nerve connections within the cochlea fail to occur in miR-96 mutants. We conclude that miR-96 regulates the progression of the physiological and morphological differentiation of cochlear hair cells and, as such, coordinates one of the most distinctive functional refinements of the mammalian auditory system.
