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

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

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 hype...

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Published in:Scientific reports Vol. 13; no. 1; p. 13813
Main Authors: Kobayashi, Misato, Kanbe, Fumi, Ishii, Reika, Tsubouchi, Hiroki, Hirai, Kana, Miyasaka, Yuki, Ohno, Tamio, Oda, Hiroaki, Ikeda, Saiko, Katoh, Hirokazu, Ichiyanagi, Kenji, Ishikawa, Akira, Murai, Atsushi, Horio, Fumihiko
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 24-08-2023
Nature Publishing Group
Nature Portfolio
Subjects:
631/45
631/45/287
692/699/317
Cardiovascular disease
Cardiovascular diseases
Cholesterol
Chromosome 2
Coronary artery disease
Dyslipidemia
Genetic analysis
Genomes
Heart diseases
High density lipoprotein
Humanities and Social Sciences
Hypertriglyceridemia
Lipids
Metabolic disorders
multidisciplinary
Nucleotide sequence
Phospholipid transfer protein
Phospholipids
Science
Science (multidisciplinary)
Sequence analysis
Serum levels
Serum lipids
Triglycerides
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Summary: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.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-40917-9