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秀丽隐杆线虫中与脊髓性肌萎缩症基因同源的smn-1缺失,会导致运动功能障碍和寿命缩短。

Deletion of smn-1, the Caenorhabditis elegans ortholog of the spinal muscular atrophy gene, results in locomotor dysfunction and reduced lifespan.

作者信息

Briese Michael, Esmaeili Behrooz, Fraboulet Sandrine, Burt Emma C, Christodoulou Stefanos, Towers Paula R, Davies Kay E, Sattelle David B

机构信息

MRC Functional Genomics Unit, Department of Physiology Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.

出版信息

Hum Mol Genet. 2009 Jan 1;18(1):97-104. doi: 10.1093/hmg/ddn320. Epub 2008 Oct 1.

Abstract

Spinal muscular atrophy is the most common genetic cause of infant mortality and is characterized by degeneration of lower motor neurons leading to muscle wasting. The causative gene has been identified as survival motor neuron (SMN). The invertebrate model organism Caenorhabditis elegans contains smn-1, the ortholog of human SMN. Caenorhabditis elegans smn-1 is expressed in various tissues including the nervous system and body wall muscle, and knockdown of smn-1 by RNA interference is embryonic lethal. Here we show that the smn-1(ok355) deletion, which removes most of smn-1 including the translation start site, produces a pleiotropic phenotype including late larval arrest, reduced lifespan, sterility as well as impaired locomotion and pharyngeal activity. Mutant nematodes develop to late larval stages due to maternal contribution of the smn-1 gene product that allows to study SMN-1 functions beyond embryogenesis. Neuronal, but not muscle-directed, expression of smn-1 partially rescues the smn-1(ok355) phenotype. Thus, the deletion mutant smn-1(ok355) provides a useful platform for functional analysis of an invertebrate ortholog of the human SMN protein.

摘要

脊髓性肌萎缩症是婴儿死亡最常见的遗传原因,其特征是下运动神经元退化导致肌肉萎缩。致病基因已被确定为生存运动神经元(SMN)。无脊椎动物模式生物秀丽隐杆线虫含有smn-1,它是人类SMN的直系同源基因。秀丽隐杆线虫的smn-1在包括神经系统和体壁肌肉在内的各种组织中表达,通过RNA干扰敲低smn-1会导致胚胎致死。在这里,我们表明smn-1(ok355)缺失,它去除了大部分smn-1包括翻译起始位点,产生了多效性表型,包括幼虫后期停滞、寿命缩短、不育以及运动和咽部活动受损。由于smn-1基因产物的母体贡献,突变线虫发育到幼虫后期阶段,这使得我们能够研究超过胚胎发育阶段的SMN-1功能。smn-1的神经元而非肌肉定向表达部分挽救了smn-1(ok355)表型。因此,缺失突变体smn-1(ok355)为人类SMN蛋白无脊椎动物直系同源基因的功能分析提供了一个有用的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5912/2644645/2399ee984f94/ddn32001.jpg

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