Identification of a Chromosome 1 Substitution Line B6-Chr1BLD as a Novel Hyperlipidemia Model <i>via</i> Phenotyping Screening
Xu Li,
Minli Sun,
Hao Qi,
Cunxiang Ju,
Zhong Chen,
Xiang Gao,
Zhaoyu Lin
Affiliations
Xu Li
State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210061, China
Minli Sun
State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210061, China
Hao Qi
GemPharmatech Inc., 12 Xuefu Road, Jiangbei New Area, Nanjing 210061, China
Cunxiang Ju
GemPharmatech Inc., 12 Xuefu Road, Jiangbei New Area, Nanjing 210061, China
Zhong Chen
GemPharmatech Inc., 12 Xuefu Road, Jiangbei New Area, Nanjing 210061, China
Xiang Gao
State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210061, China
Zhaoyu Lin
State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210061, China
Hyperlipidemia is a chronic disease that seriously affects human health. Due to the fact that traditional animal models cannot fully mimic hyperlipidemia in humans, new animal models are urgently needed for basic drug research on hyperlipidemia. Previous studies have demonstrated that the genomic diversity of the wild mice chromosome 1 substitution lines was significantly different from that of laboratory mice, suggesting that it might be accompanied by phenotypic diversity. We first screened the blood lipid-related phenotype of chromosome 1 substitution lines. We found that the male HFD-fed B6-Chr1BLD mice showed more severe hyperlipidemia-related phenotypes in body weight, lipid metabolism and liver lesions. By RNA sequencing and whole-genome sequencing results of B6-Chr1BLD, we found that several differentially expressed single nucleotide polymorphism enriched genes were associated with lipid metabolism-related pathways. Lipid metabolism-related genes, mainly including Aida, Soat1, Scly and Ildr2, might play an initial and upstream role in the abnormal metabolic phenotype of male B6-Chr1BLD mice. Taken together, male B6-Chr1BLD mice could serve as a novel, polygenic interaction-based hyperlipidemia model. This study could provide a novel animal model for accurate clinical diagnosis and precise medicine of hyperlipidemia.
