
Khdc3 유전자 돌연변이가 있는 조상을 가진 야생형 마우스에서 간 대사 유전자의 지속적인 발현 이상이 관찰되며, 이는 DNA 변이 없이도 세대를 거쳐 전달된다.


coremsg

Genetic variants can alter the profile of heritable molecules such as small RNAs in sperm and oocytes, and in this manner ancestral genetic variants can have a significant effect on offspring phenotypes even if they are not themselves inherited. Here we show that wild type female mice descended from ancestors with a mutation in the mammalian germ cell gene Khdc3 have hepatic metabolic defects that persist over multiple generations. We find that genetically wild type females descended from Khdc3 mutants have transcriptional dysregulation of critical hepatic metabolic genes, which persist over multiple generations and pass through both female and male lineages. This was associated with dysregulation of hepatically-metabolized molecules in the blood of these wild type mice with mutational ancestry. The oocytes of Khdc3 -null females, as well as their wild type descendants, had dysregulation of multiple small RNAs, suggesting that these epigenetic changes in the gametes transmit the phenotype between generations. Our results demonstrate that ancestral mutation in Khdc3 can produce transgenerational inherited phenotypes, potentially indefinitely.

### Competing Interest Statement

The authors have declared no competing interest.

Khdc3 Regulates Metabolism Across Generations in a DNA-Independent Manner

유전자-변이가-없어도-후대에-대사-이상이-지속되는-현상-khdc3-유전자-돌연변이의-초세대-영향


유전자 변이가 없어도 후대에 대사 이상이 지속되는 현상: Khdc3 유전자 돌연변이의 초세대 영향
