Forward genetic screen for Caenorhabditis elegans mutants with a shortened locomotor healthspan
Forward genetic screen for Caenorhabditis elegans mutants with a shortened locomotor healthspan
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对运动健康寿命缩短的秀丽隐杆线虫突变体进行正向遗传筛选
DOI：
10.1101/487876
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Maruyama Ichiro N.
中科院分区：
文献类型：
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作者：
Kawamura Kazuto;Maruyama Ichiro N.
遗传突变并不总是立即有毒。一些突变在青年时期引起症状，而其他突变在成年期引起症状。表现出延迟发病的疾病症状的突变动物可以提供对在成年期维持功能能力的机制的见解。在这里，我们利用线虫秀丽隐杆线虫相对较短的寿命，并开发了一种新的筛选程序，以收集在成年后明显存在运动缺陷的突变体。经甲磺酸乙酯诱变后，我们分离到5个C。逐渐失去成年运动活性的优雅品系。在其中一种突变株中，延伸体复合蛋白组分2（elpc-2）中的无义突变导致运动功能进行性下降。C. elpcmutants也不能在成年期维持运动功能，表明Elongator复合体在维持C.两个寿命相同的人不一定有相同的健康寿命。一个人可能会保留运动和认知功能，直到生命的尽头，而另一个人可能会在成年后失去它们。目前，调节健康寿命的基因网络在很大程度上是未知的。无偏见地寻找在成年期维持功能能力的基因可能会发现健康寿命的关键调节因子。在这里，我们分离出五种在成年后逐渐失去运动功能的秀丽隐杆线虫菌株。突变分析表明，延长复合体调节运动健康。在本筛选中鉴定的突变体和突变可以提供对与年龄相关的运动障碍的机制的见解，并且可以提供改善健康寿命的线索。
An inherited mutation is not always immediately toxic. Some mutations cause symptoms during youth, while other mutations cause symptoms during adulthood. Mutant animals that show delayed onset of disease symptoms may provide insights into mechanisms that maintain functional capacities during adulthood. Here, we take advantage of the relatively short lifespan of the nematodeCaenorhabditis elegansand develop a novel screening procedure to collect mutants with locomotor deficits that become apparent in adulthood. After ethyl methanesulfonate mutagenesis, we isolated fiveC. elegansmutant strains that progressively lose adult locomotor activity. In one of the mutant strains, a nonsense mutation in Elongator Complex Protein Component 2 (elpc-2) causes a progressive decline in locomotor function. OtherC. elegans elpcmutants were also unable to maintain locomotor function during adulthood, indicating that the Elongator complex plays a critical role in maintaining locomotor healthspan inC. elegans.Significance StatementTwo people with the same lifespan do not necessarily have the same healthspan. One person may retain locomotor and cognitive functions until the end of life, while another person may lose them during adulthood. Currently, the network of genes that regulate healthspan is largely unknown. Unbiased searches for genes that work to maintain functional capacities during adulthood may uncover key regulators of healthspan. Here we isolated fiveCaenorhabditis elegansmutant strains that progressively lose their locomotor function in adulthood. Mutant analysis suggests that the Elongator complex regulates locomotor healthspan. Mutants and mutations identified in the present screen may provide insights into mechanisms of age-related locomotor impairment and may provide clues for improving healthspan.