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与miR-96突变小鼠diminuendo耳聋表型的特定特征相关的Ptprq减少。

A reduction in Ptprq associated with specific features of the deafness phenotype of the miR-96 mutant mouse diminuendo.

作者信息

Chen Jing, Johnson Stuart L, Lewis Morag A, Hilton Jennifer M, Huma Andreea, Marcotti Walter, Steel Karen P

机构信息

Wellcome Trust Sanger Institute, Cambridge, UK; Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London, SE1 1UL, UK.

出版信息

Eur J Neurosci. 2014 Mar;39(5):744-56. doi: 10.1111/ejn.12484. Epub 2014 Jan 22.

Abstract

miR-96 is a microRNA, a non-coding RNA gene which regulates a wide array of downstream genes. The miR-96 mouse mutant diminuendo exhibits deafness and arrested hair cell functional and morphological differentiation. We have previously shown that several genes are markedly downregulated in the diminuendo organ of Corti; one of these is Ptprq, a gene known to be important for maturation and maintenance of hair cells. In order to study the contribution that downregulation of Ptprq makes to the diminuendo phenotype, we carried out microarrays, scanning electron microscopy and single hair cell electrophysiology to compare diminuendo mutants (heterozygous and homozygous) with mice homozygous for a functional null allele of Ptprq. In terms of both morphology and electrophysiology, the auditory phenotype of mice lacking Ptprq resembles that of diminuendo heterozygotes, while diminuendo homozygotes are more severely affected. A comparison of transcriptomes indicates there is a broad similarity between diminuendo homozygotes and Ptprq-null mice. The reduction in Ptprq observed in diminuendo mice appears to be a major contributor to the morphological, transcriptional and electrophysiological phenotype, but does not account for the complete diminuendo phenotype.

摘要

miR-96是一种微小RNA,即一种调控众多下游基因的非编码RNA基因。miR-96小鼠突变体diminuendo表现出耳聋以及毛细胞功能和形态分化停滞。我们之前已经表明,在diminuendo耳蜗器官中有几个基因显著下调;其中之一是Ptprq,该基因已知对毛细胞的成熟和维持很重要。为了研究Ptprq下调对diminuendo表型的影响,我们进行了微阵列分析、扫描电子显微镜检查和单毛细胞电生理学研究,以比较diminuendo突变体(杂合子和纯合子)与Ptprq功能性无效等位基因纯合的小鼠。在形态学和电生理学方面,缺乏Ptprq的小鼠的听觉表型类似于diminuendo杂合子,而diminuendo纯合子受影响更严重。转录组比较表明,diminuendo纯合子和Ptprq基因敲除小鼠之间存在广泛的相似性。在diminuendo小鼠中观察到的Ptprq减少似乎是形态学、转录和电生理学表型的主要促成因素,但不能解释完整的diminuendo表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b689/4065360/fc89b7db8c20/ejn0039-0744-f1.jpg

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