Primary Genetic Investigation of a Hyperlipidemia Model : Molecular Characteristics and Variants of the Apolipoprotein E Gene in Mongolian Gerbil

Abstract EN

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.