Chair for Molecular Animal Breeding and Biotechnology, Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, 81377 Munich, Germany.
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Genes (Basel). 2021 Oct 29;12(11):1732. doi: 10.3390/genes12111732.
(transient receptor potential cation channel, subfamily C, member 7; 862 amino acids) knockout mice are described showing no clear phenotypic alterations, therefore, the functional relevance of the gene remains unclear. A complementary approach for the functional analysis of a given gene is the examination of individuals harbouring a mutant allele of the gene. In the phenotype-driven Munich ENU mouse mutagenesis project, a high number of phenotypic parameters was used for establishing novel mouse models on the genetic background of C3H inbred mice. The phenotypically dominant mutant line SMA002 was established and further examined. Analysis of the causative mutation as well as the phenotypic characterization of the mutant line were carried out. The causative mutation was detected in the gene which leads to the production of a truncated protein due to the novel stop codon at amino acid position 810 thereby affecting the highly conserved cytoplasmic C terminus of the protein. heterozygous mutant mice of both sexes were viable and fertile, but showed distinct morphological and behavioural alterations which is in contrast to the published phenotype of knockout mice. Thus, the mutation leads to a dominant negative effect of the mutant protein.
瞬时受体电位阳离子通道亚家族 C，成员 7（862 个氨基酸）基因敲除小鼠表型无明显改变，因此，该基因的功能相关性尚不清楚。研究特定基因功能的一种补充方法是研究携带该基因突变的个体。在表型驱动的慕尼黑ENU 小鼠诱变项目中，在 C3H 近交系小鼠的遗传背景下，使用大量表型参数建立了新型小鼠模型。表型显性突变系 SMA002 已经建立并进一步进行了研究。对突变基因的致病突变进行了分析，并对突变系的表型特征进行了研究。在基因中检测到致病突变，导致在氨基酸位置 810 产生新的终止密码子，从而产生截断蛋白，从而影响蛋白高度保守的细胞质 C 末端。该基因的杂合突变小鼠在两性中均具有生存能力和繁殖力，但表现出明显的形态和行为改变，这与先前报道的基因敲除小鼠表型相反。因此，该突变导致突变蛋白的显性负效应。
