Zhen Wang 1 , Jifeng Zhang 2 , Hong Li 1 , Junyi Li 1 , Manabu Niimi 3 , Guohui Ding 1 , 4 , Haifeng Chen 4 , 5 , Jie Xu 2 , Hongjiu Zhang 6 , Ze Xu 7 , Yulin Dai 8 , 9 , Tuantuan Gui 8 , 9 , Shengdi Li 8 , 9 , Zhi Liu 8 , 9 , Sujuan Wu 4 , 10 , Mushui Cao 4 , 11 , Lu Zhou 8 , 9 , Xingyu Lu 5 , Junxia Wang 5 , Jing Yang 4 , 10 , Yunhe Fu 8 , 9 , Dongshan Yang 2 , Jun Song 2 , Tianqing Zhu 2 , Shen Li 3 , Bo Ning 3 , Ziyun Wang 3 , Tomonari Koike 12 , Masashi Shiomi 12 , Enqi Liu 13 , 14 , Luonan Chen 8 , Jianglin Fan a , 3 , 14 , Y. Eugene Chen b , 2 , Yixue Li c , 1 , 4 , 5 , 10 , 11
01 June 2016
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.