The genetic basis for susceptibility to Rift Valley fever disease in MBT/Pas mice

被引：12
作者：
Tokuda, S. [1 ,2 ]
Do Valle, T. Z. [1 ,2 ,3 ]
Batista, L. [1 ,2 ,4 ]
Simon-Chazottes, D. [1 ,2 ]
Guillemot, L. [1 ,2 ]
Bouloy, M. [5 ]
Flamand, M. [6 ]
Montagutelli, X. [1 ,2 ]
Panthier, J-J [1 ,2 ]
机构：
[1] Inst Pasteur, Dev & Stem Cell Biol Dept, Mouse Funct Genet, F-75724 Paris, France
[2] CNRS, URA 2578, Paris, France
[3] Fiocruz MS, Inst Oswaldo Cruz, Lab Imunomodulacao & Protozool, BR-21045900 Rio De Janeiro, Brazil
[4] Univ Paris 06, Sorbonne Univ, IFD, Paris, France
[5] Inst Pasteur, Bunyaviruses Mol Genet, F-75724 Paris, France
[6] Inst Pasteur, Struct Virol, F-75724 Paris, France
来源：
GENES AND IMMUNITY | 2015年 / 16卷 / 03期
关键词：
INBRED RAT STRAINS; MOUSE MODEL; SALMONELLA-TYPHIMURIUM; NORTHEASTERN KENYA; VIRUS-INFECTION; PATHOGENESIS; RESISTANCE; BUNYAVIRIDAE; NSS; ASSOCIATION;
D O I：
10.1038/gene.2014.79
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
The large variation in individual response to infection with Rift Valley fever virus (RVFV) suggests that host genetic determinants play a role in determining virus-induced disease outcomes. These genetic factors are still unknown. The systemic inoculation of mice with RVFV reproduces major pathological features of severe human disease, notably the hepatitis and encephalitis. A genome scan performed on 546 (BALB/c xMBT) F2 progeny identified three quantitative trait loci (QTLs), denoted Rvfs-1 to Rvfs-3, that were associated with disease susceptibility in MBT/Pas mice. Non-parametric interval-mapping revealed one significant and two suggestive linkages with survival time on chromosomes 2 (Rvfs-1), 5 (Rvfs-3) and 11 (Rvfs-2) with respective logarithm of odds (LOD) scores of 4.58, 2.95 and 2.99. The two-part model, combining survival time and survival/death, identified one significant linkage to Rvfs-2 and one suggestive linkage to Rvfs-1 with respective LOD scores of 5.12 and 4.55. Under a multiple model, with additive effects and sex as a covariate, the three QTLs explained 8.3% of the phenotypic variance. Sex had the strongest influence on susceptibility. The contribution of Rvfs-1, Rvfs-2 and Rvfs-3 to survival time of RVFV-infected mice was further confirmed in congenic mice.
引用
收藏
页码：206 / 212
页数：7
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