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首页> 外文期刊>Disease models & mechanisms: DMM >Modelling brain dopamine-serotonin vesicular transport disease in Caenorhabditis elegans
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Modelling brain dopamine-serotonin vesicular transport disease in Caenorhabditis elegans

机译：秀丽隐杆线虫脑多巴胺-5-羟色胺水泡运输疾病的建模

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Brain dopamine-serotonin vesicular transport disease is a rare disease caused by autosomal recessive mutations in the SLC18A2 gene, which encodes the VMAT2 protein. VMAT2 is a membrane protein responsible for vesicular transport of monoamines, and its disruption negatively affects neurotransmission. This results in a severe neurodevelopmental disorder affecting motor skills and development, and causes muscular hypotonia. The condition was initially described in a consanguineous Saudi Arabian family with affected siblings homozygous for a P387L mutation. We subsequently found a second mutation in a New Zealand family (homozygous P237H), which was later also identified in an Iraqi family. Pramipexole has been shown to have some therapeutic benefit. Transgenic Caenorhabditis elegans were developed to model the P237H and P387L mutations. Investigations into dopamine- and serotonin-related C. elegans phenotypes, including pharyngeal pumping and grazing, showed that both mutations cause significant impairment of these processes when compared with a non-transgenic N2 strain and a transgenic containing the wild-type human SLC18A2 gene. Preliminary experiments investigating the therapeutic effects of serotonin and pramipexole demonstrated that serotonin could successfully restore the pharyngeal pumping phenotype. These analyses provide further support for the role of these mutations in this disease.
机译：脑多巴胺-5-羟色胺水泡运输疾病是由SLC18A2基因的常染色体隐性突变引起的罕见疾病，该基因编码VMAT2蛋白。 VMAT2是负责单胺水泡运输的膜蛋白，其破坏会对神经传递产生负面影响。这会导致严重的神经发育障碍，影响运动技能和发育，并导致肌张力低下。该病最初是在一个近亲的沙特阿拉伯家庭中描述的，其同胞对P387L突变是纯合的。随后，我们在一个新西兰家庭（纯合子P237H）中发现了第二个突变，后来在一个伊拉克家庭中也发现了该突变。已显示普拉克索具有一定的治疗益处。开发了转基因秀丽隐杆线虫以模拟P237H和P387L突变。对多巴胺和5-羟色胺相关的秀丽隐杆线虫表型的研究（包括咽抽和放牧）显示，与非转基因N2菌株和含有野生型人SLC18A2基因的转基因相比，这两种突变均会导致这些过程的重大损伤。研究5-羟色胺和普拉克索的治疗效果的初步实验表明，5-羟色胺可以成功地恢复咽抽动表型。这些分析为这些突变在该疾病中的作用提供了进一步的支持。

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