title: Primary genetic investigation of a hyperlipidemia model: molecular characteristics and variants of the apolipoprotein E gene in Mongolian gerbil.
abstract: The objective of this work was to establish a novel Mongolian gerbil (Meriones unguiculatus) hyperlipidemia model and to investigate its susceptibility genetic basis. Two rodent (gerbil and rat) hyperlipidemia models were induced by feeding a high fat/high-cholesterol (HF/HC) diet. There were significant increases of serum total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in gerbils within a 4-week modeling period. About 10-30% of >8-month-old individuals developed hyperlipidemia spontaneously. The apolipoprotein E (ApoE) gene was cloned by merging a sequence of rapid amplification of cDNA ends (RACE) and nested polymerase chain reaction products. The results revealed an open reading frame of 948 bp, encoding a protein of 298 amino acids. The gene without a 5'-UTR region in the first intron was highly homologous to human Apo-A-I and rat Apo-A-IV. The distribution of expression of the ApoE gene in liver, brain, heart, lung, kidney, and adrenal gland was detected by an ABC immunohistochemical procedure. Three single nucleotide polymorphisms (SNPs; C97T, G781T, and A1774T) were first found using PCR-single-strand conformation polymorphism (PCR-SSCP) in a closed population containing 444 animals. Correlation analysis confirmed that new SNPs, age, and gender were associated significantly (P < 0.05) with hyperlipidemia.
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China ; Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Yuehuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jiusheng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Qiaojuan
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Guo
authors.affiliation: Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Huazhong
authors.initials: H
authors.lastname: Ying
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Ningying
authors.initials: N
authors.lastname: Xu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D016678:Genome / Q000235:genetics; D005849:Gerbillinae / Q000235:genetics*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics* / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics; D019655:Quantitative Trait, Heritable; D017207:Rats, Sprague-Dawley; D017422:Sequence Analysis, DNA
chemical_list: D001057:Apolipoproteins E