Comparative transcriptomics reveals specific responding genes associated with atherosclerosis in rabbit and mouse models

Abstract

Mouse and rabbit are frequently employed species for atherosclerosis research. With respect to modeling human atherosclerosis, it has been observed that variations in phenotype under commonly used atherogenic conditions are partial or no congruence between two species. However, genome-wide molecular variations are still lacking. To understand the differences between rabbit and mouse in developing atherosclerosis, here from aspect of orthologs, we compared the genome-wide expression profiles of two species under the same atherosclerosis driven factors: high-fat diet or LDLR deficiency. Our results illuminated that: 1) LDLR-deficiency induced different gene expression changes in rabbit and mouse. WHHL rabbit had more significantly differential expressed genes and the most of genes were down-regulated. 2) Some genes and functions were commonly dysregulated in high-fat fed rabbit and mouse models, such as lipid metabolism and inflammation process. However, high-fat intake in rabbit produced more differentially expressed genes and more serious functional effects. 3) Specific differential expression genes were revealed for rabbit and mouse related with high-fat intake. In the aspect of lipoprotein metabolism, APOA4 and APOB was the major responding gene in rabbit and mice, respectively. The expression change of APOA4 and APOB in human atherosclerosis was more similar to rabbit, and therefore rabbit might be a better animal model for investigating human lipoprotein metabolism related diseases. In conclusion, our comparative transcriptome analysis revealed species-specific expression regulation that could partially explain the different phenotypes between rabbit and mouse, which was helpful for model selection to study atherosclerosis.

A single workflow for multi-species blood transcriptomics

“…For a standardized analysis, the volume of blood collected may vary between different species [ 5 , 6 ]. In small animals, the volume of blood that is practical to sample is often lower than in larger animals and humans, or lower in case of longitudinal studies due to repeated sampling [ 7 , 8 ]. It is of importance to stabilize the collected blood as soon as possible [ 9 – 11 ], (i) to limit degradation of RNA, (ii) to minimize the risk of non-specific cell activation, and (iii) to allow for sample investigation several days or months later and/or at another analysis laboratory [ 12 ].…”

Distinct Retrotransposon Evolution Profile in the Genome of Rabbit (Oryctolagus cuniculus)

“…Rabbits are monogastric herbivores, widely distributed around the globe and used in the production of meat, fur, and wool, particularly in China. In addition, rabbits are among the most common experimental animals in biomedical studies because of their moderate size, gentle disposition, superior reproductive performance, short life span, and their generational gap ( Wang et al 2017 ; Fan et al 2018 ; Ma et al 2018 ; Wu et al 2018 ). The genome of the rabbit was firstly sequenced and assembled (Orycun 2.0, 2.66 Gb) in 2014.…”