关键词: 3ʹUTR BH3-only EGL-1 EHT 1864 EHT 8560 NMD Pak SMG-1 nonsense-mediated decay small GTPase

Mesh : Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins

来  源:   DOI:10.1093/g3journal/jkab234   PDF(Pubmed)

Abstract:
Using model organisms to identify novel therapeutic targets is frequently constrained by pre-existing genetic toolkits. To expedite positive selection for identification of novel downstream effectors, we engineered conditional expression of activated CED-10/Rac to disrupt Caenorhabditis elegans embryonic morphogenesis, titrated to 100% lethality. The strategy of engineering thresholds for positive selection using experimental animals was validated with pharmacological and genetic suppression and is generalizable to diverse molecular processes and experimental systems.
摘要:
使用模型生物来鉴定新的治疗靶标经常受到预先存在的遗传工具包的限制。为了加快识别新的下游效应物的正向选择,我们设计了激活的CED-10/Rac的条件表达,以破坏秀丽隐杆线虫的胚胎形态发生,滴定到100%的杀伤力.使用实验动物进行正向选择的工程阈值策略已通过药理学和遗传抑制得到验证,并且可推广到各种分子过程和实验系统。
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