G3: Genes, Genomes, Genetics ( IF 2.1 ) Pub Date : 2020-10-27 , DOI: 10.1534/g3.120.401720 Wendy A Alcaraz 1 , Zheng Liu 1 , Phoebe Valdes 1 , Edward Chen 1 , Alan G Valdovino Gonzalez 1 , Shelby Wade 1 , Cinny Wong 1 , Eunnie Kim 1 , Hsiang-Hua M Chen 1 , Alison Ponn 1 , Dorothy Concepcion 1 , Bruce A Hamilton 2
Zfp423 encodes a transcriptional regulatory protein that interacts with canonical signaling and lineage pathways. Mutations in mouse Zfp423 or its human ortholog ZNF423 are associated with a range of developmental abnormalities reminiscent of ciliopathies, including cerebellar vermis hypoplasia and other midline brain defects. Null mice have reduced viability in most strain backgrounds. Here we show complete lethality on a C57BL/6J background, dominant rescue in backcrosses to any of 13 partner strains, with strain-dependent survival frequencies, and evidence for a BALB/c-derived survival modifier locus on chromosome 5. Survival data indicate both perinatal and postnatal periods of lethality. Anatomical data from a hypomorphic gene trap allele observed on both C57BL/6J and BALB/c congenic backgrounds shows an aggregate effect of background on sensitivity to Zfp423 loss rather than a binary effect on viability.
中文翻译:
应变依赖的修饰基因决定Zfp423小鼠的生存。
Zfp423编码与规范性信号传导和谱系途径相互作用的转录调节蛋白。小鼠Zfp423或其人类直系同源物ZNF423中的突变与许多发展异常相关,令人联想到纤毛病,包括小脑ver部发育不全和其他中线大脑缺陷。空小鼠在大多数菌株背景中的活力降低。在这里,我们显示了在C57BL / 6J背景下的完全杀伤力,与13个配对菌株中的任何一个的回交占优势,并具有取决于菌株的存活频率,并显示了5号染色体上BALB / c衍生的存活修饰位点。围产期和产后致死期。在C57BL / 6J和BALB / c同基因背景上观察到的亚型基因陷阱等位基因的解剖数据显示,背景对Zfp423缺失敏感性的聚集效应,而不是对生存力的二元效应。