Scientific Reports (Aug 2023)

C3H/HeNSlc mouse with low phospholipid transfer protein expression showed dyslipidemia

  • Misato Kobayashi,
  • Fumi Kanbe,
  • Reika Ishii,
  • Hiroki Tsubouchi,
  • Kana Hirai,
  • Yuki Miyasaka,
  • Tamio Ohno,
  • Hiroaki Oda,
  • Saiko Ikeda,
  • Hirokazu Katoh,
  • Kenji Ichiyanagi,
  • Akira Ishikawa,
  • Atsushi Murai,
  • Fumihiko Horio

DOI
https://doi.org/10.1038/s41598-023-40917-9
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 11

Abstract

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Abstract High serum levels of triglycerides (TG) and low levels of high-density lipoprotein cholesterol (HDL-C) increase the risk of coronary heart disease in humans. Herein, we first reported that the C3H/HeNSlc (C3H-S) mouse, a C3H/HeN-derived substrain, is a novel model for dyslipidemia. C3H-S showed hypertriglyceridemia and low total cholesterol (TC), HDL-C, and phospholipid (PL) concentrations. To identify the gene locus causing dyslipidemia in C3H-S, we performed genetic analysis. In F2 intercrosses between C3H-S mice and strains with normal serum lipids, the locus associated with serum lipids was identified as 163–168 Mb on chromosome 2. The phospholipid transfer protein (Pltp) gene was a candidate gene within this locus. Pltp expression and serum PLTP activity were markedly lower in C3H-S mice. Pltp expression was negatively correlated with serum TG and positively correlated with serum TC and HDL-C in F2 mice. Genome sequencing analysis revealed that an endogenous retrovirus (ERV) sequence called intracisternal A particle was inserted into intron 12 of Pltp in C3H-S. These results suggest that ERV insertion within Pltp causes aberrant splicing, leading to reduced Pltp expression in C3H-S. This study demonstrated the contribution of C3H-S to our understanding of the relationship between TG, TC, and PL metabolism via PLTP.