| First Author | Rodríguez JM | Year | 2013 |
| Journal | Circ Res | Volume | 113 |
| Issue | 9 | Pages | 1054-64 |
| PubMed ID | 23948654 | Mgi Jnum | J:221553 |
| Mgi Id | MGI:5640944 | Doi | 10.1161/CIRCRESAHA.113.302052 |
| Citation | Rodriguez JM, et al. (2013) Altered expression of Raet1e, a major histocompatibility complex class 1-like molecule, underlies the atherosclerosis modifier locus Ath11 10b. Circ Res 113(9):1054-64 |
| abstractText | RATIONALE: Quantitative trait locus mapping of an intercross between C57.Apoe(-)/(-) and FVB.Apoe(-)/(-) mice revealed an atherosclerosis locus controlling aortic root lesion area on proximal chromosome 10, Ath11. In a previous work, subcongenic analysis showed Ath11 to be complex with proximal (10a) and distal (10b) regions. OBJECTIVE: To identify the causative genetic variation underlying the atherosclerosis modifier locus Ath11 10b. METHODS AND RESULTS: We now report subcongenic J, which narrows the 10b region to 5 genes, Myb, Hbs1L, Aldh8a1, Sgk1, and Raet1e. Sequence analysis of these genes revealed no amino acid coding differences between the parental strains. However, comparing aortic expression of these genes between F1.Apoe(-)/(-) Chr10SubJ((B/F)) and F1.Apoe(-)/(-) Chr10SubJ((F/F)) uncovered a consistent difference only for Raet1e, with decreased, virtually background, expression associated with increased atherosclerosis in the latter. The key role of Raet1e was confirmed by showing that transgene-induced aortic overexpression of Raet1e in F1.Apoe(-)/(-) Chr10SubJ((F/F)) mice decreased atherosclerosis. Promoter reporter constructs comparing C57 and FVB sequences identified an FVB mutation in the core of the major aortic transcription start site abrogating activity. CONCLUSIONS: This nonbiased approach has revealed Raet1e, a major histocompatibility complex class 1-like molecule expressed in lesional aortic endothelial cells and macrophage-rich regions, as a novel atherosclerosis gene and represents one of the few successes of the quantitative trait locus strategy in complex diseases. |
