Altered Expression of Raet1e, a Major Histocompatibility Complex Class 1-Like Molecule, Underlies the Atherosclerosis Modifier Locus Ath11 10bopen access
- Authors
- Rodriguez, Jose M.; Wolfrum, Susanne; Robblee, Megan; Chen, Kwan Y.; Gilbert, Zachary N.; Choi, Jae-Hoon; Teupser, Daniel; Breslow, Jan L.
- Issue Date
- Oct-2013
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Keywords
- atherosclerosis; gene expression; genetic susceptibility; mice; mouse model; quantitative trait loci
- Citation
- CIRCULATION RESEARCH, v.113, no.9, pp.1054 - 1064
- Indexed
- SCIE
SCOPUS
- Journal Title
- CIRCULATION RESEARCH
- Volume
- 113
- Number
- 9
- Start Page
- 1054
- End Page
- 1064
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/161863
- DOI
- 10.1161/CIRCRESAHA.113.302052
- ISSN
- 0009-7330
- Abstract
- 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.
- Files in This Item
-
- Appears in
Collections - 서울 자연과학대학 > 서울 생명과학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/161863)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.