Two imprinted gene mutations: three phenotypes
Two imprinted gene mutations: three phenotypes
复制标题
DOI：
10.1093/oxfordjournals.hmg.a018917
复制
发表时间：
2000-09-22
影响因子：
3.5
通讯作者：
Rasberry, C
中科院分区：
文献类型：
--
作者：
Cattanach, BM;Peters, J;Rasberry, C
已经在小鼠中产生印迹基因的遗传修饰以研究其表达的调节。它们表现出典型的印记基因遗传。在这里，我们描述了两个印迹基因突变诱变实验。其中一种只有在通过男性传播时才会表达。它导致产前生长迟缓，这类似于Igf 2敲除，并映射到7号染色体上的基因座附近。与敲除的差异包括异常头部表型、纯合致死性和无法挽救Tme（Igf 2 r缺陷）致死性，表明lgf 2本身可能不受直接影响。第二个突变映射接近远端2号染色体上的印记基因的Gnas簇。它给出了两个不同的表型，根据父母的起源，一个严重的新生儿水肿与微心和出生后的生长迟缓。水肿表型是有效致死的，并且类似于具有远端2号染色体的父系部分二体性的小鼠以及具有母系来源的Gnas外显子2敲除的小鼠。然而，第二种生长迟缓表型不同于母本部分二体性和父本基因敲除的表型。提供了一个假设来解释与基于Nesp/Nespas有义/反义和Gnasxl转录本的Gnas簇中的三种基因型相关的表型。
Genetic modifications of imprinted genes have been generated in the mouse to investigate the regulation of their expression. They show classical imprinted gene inheritances. Here we describe two imprinted gene mutations deriving from mutagenesis experiments. One is expressed only when transmitted through males. It causes a prenatal growth retardation which resembles that of the Igf2 knockout and maps close to the locus on chromosome 7. Differences from the knockout, which include an abnormal head phenotype, homozygous lethality, and an inability to rescue a Tme (Igf2r-deficient) lethality, suggest that lgf2 itself may not be directly affected. The second mutation maps close to the Gnas cluster of imprinted genes on distal chromosome 2. It gives two distinct phenotypes according to parental origin, a gross neonatal oedema with microcardia and a postnatal growth retardation. The oedema phenotype is effectively lethal and resembles that of mice with paternal partial disomy for distal chromosome 2, as well as that of mice having a maternally derived Gnas exon 2 knockout. However, the second growth retardation phenotype differs from that of the maternal partial disomy and the paternal knockout. A hypothesis to explain the phenotypes associated with the three genotypes based on the Nesp/Nespas sense/antisense and Gnasxl transcripts in the Gnas cluster is offered.