Key result
WHHL and cholesterol-fed rabbits exhibited similar inflammatory gene expression profiles in the aorta, but only cholesterol-fed rabbits showed pronounced inflammatory responses and abnormal lipid metabolism in the liver.
Whole-genome and transcriptome profiling of rabbit models reveals distinct hepatic inflammatory and lipid metabolism responses between genetic and diet-induced hypercholesterolemia, despite similar aortic gene expression.
Provides foundational genomic data for hyperlipidemic rabbit models; leaves open translation to human atherosclerosis research.
The rabbit (Oryctolagus cuniculus) is an important experimental animal for studying human diseases, such as hypercholesterolemia and atherosclerosis. Despite this, genetic information and RNA expression profiling of laboratory rabbits are lacking. Here, we characterized the whole-genome variants of three breeds of the most popular experimental rabbits, New Zealand White (NZW), Japanese White (JW) and Watanabe heritable hyperlipidemic (WHHL) rabbits. Although the genetic diversity of WHHL rabbits was relatively low, they accumulated a large proportion of high-frequency deleterious mutations due to the small population size. Some of the deleterious mutations were associated with the pathophysiology of WHHL rabbits in addition to the LDLR deficiency. Furthermore, we conducted transcriptome sequencing of different organs of both WHHL and cholesterol-rich diet (Chol)-fed NZW rabbits. We found that gene expression profiles of the two rabbit models were essentially similar in the aorta, even though they exhibited different types of hypercholesterolemia. In contrast, Chol-fed rabbits, but not WHHL rabbits, exhibited pronounced inflammatory responses and abnormal lipid metabolism in the liver. These results provide valuable insights into identifying therapeutic targets of hypercholesterolemia and atherosclerosis with rabbit models.
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Wang et al. (2016) studied Hypercholesterolemia and atherosclerosis (n=42). WHHL genetic model and cholesterol-rich diet vs. Wild-type rabbits on standard chow diet was evaluated on Whole-genome variants and differentially expressed genes (DEGs) in aorta and liver. WHHL and cholesterol-fed rabbits exhibited similar inflammatory gene expression profiles in the aorta, but only cholesterol-fed rabbits showed pronounced inflammatory responses and abnormal lipid metabolism in the liver.
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