Department of Genetics and Evolution, University of Geneva, 1211 Geneva 4, Switzerland.
School of Life Sciences, Federal Institute of Technology, Lausanne (EPFL), 1015 Lausanne, Switzerland.
Proc Natl Acad Sci U S A. 2017 Oct 31;114(44):E9290-E9299. doi: 10.1073/pnas.1712511114. Epub 2017 Oct 17.
During embryonic development, genes participate in the building of a functional digestive system in metazoans, and genetic conditions involving these genes lead to important, sometimes lethal, growth retardation. Recently, this phenotype was obtained after deletion of , the antisense growth-associated long noncoding RNA (lncRNA) located between and In this study, we have analyzed the function of genes in delayed growth trajectories by looking at several nested targeted deficiencies of the mouse cluster. Mutant pups were severely stunted during the suckling period, but many recovered after weaning. After comparing seven distinct alleles, including CRISPR/Cas9 deletions involving , we identified as the critical component for the gut to maintain milk-digestive competence. This essential function could be abrogated by the dominant-negative effect of as shown by a genetic rescue approach, thus further illustrating the importance of posterior prevalence in gene function. A role for the lncRNA in the control of postnatal growth could not be corroborated.
在胚胎发育过程中,基因参与构建后生动物的功能性消化系统,涉及这些基因的遗传条件会导致重要的、有时甚至是致命的生长迟缓。最近,在删除位于和之间的反义生长相关长非编码 RNA (lncRNA) 后,获得了这种表型。在这项研究中,我们通过研究小鼠基因簇的几个嵌套靶向缺失,分析了基因在生长轨迹延迟中的功能。突变幼崽在哺乳期严重发育迟缓,但许多幼崽在断奶后恢复正常。在比较了包括涉及的 CRISPR/Cas9 缺失在内的七个不同的等位基因后,我们确定作为肠道维持奶消化能力的关键组成部分。通过遗传挽救方法显示,作为显性负效应的 可以消除这种必需功能,从而进一步说明了在后头侧优势在基因功能中的重要性。lncRNA 在控制出生后生长中的作用无法得到证实。