The Bcg/Ity/Lsh locus: genetic transfer of resistance to infections in C57BL/6J mice transgenic for the Nramp1 Gly169 allele
The Bcg/Ity/Lsh locus: genetic transfer of resistance to infections in C57BL/6J mice transgenic for the Nramp1 Gly169 allele
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Bcg/Ity/Lsh 基因座：Nramp1 Gly169 等位基因转基因 C57BL/6J 小鼠抗感染性的遗传转移
作者：
G. Govoni;Silvia Vidal;S. Gauthier;E. Skamene;D. Malo;P. Gros
The murine Bcg/Ity/Lsh locus determines the susceptibilities of inbred strains to infection with unrelated intracellular parasites, such as Mycobacterium bovis, Salmonella typhimurium, and Leishmania donovani. A candidate for Bcg/Ity/Lsh, designated Nramp1, has been recently identified and shown to encode a novel integral membrane protein that is expressed exclusively in professional phagocytes but whose function remains unknown. In inbred strains, the susceptibility to infection is associated with a single glycine-to-aspartic acid substitution at position 169 (G169D) in the predicted TM4 of the protein. To confirm the candidacy of Nramp1 as Bcg/Ity/Lsh and to determine the importance of the G169D mutation on Nramp1 function, we constructed transgenic mice in which the G169 allele of Nramp1 was transferred onto the background of a homozygous D169 allele. These transgenic mice were analyzed for their sensitivity to infections under the control of Bcg/Ity/Lsh. The transgene constructed for these studies contained the entire Nramp1G169 gene together with approximately 5 kb of sequences upstream of the transcription initiation site of this gene. We observed that these sequences were sufficient to direct Nramp1G169 expression in transgenic macrophages, resulting in the appearance of a mature protein of 90 to 100 kDa over a background of Nramp1G169 characterized by the complete absence of the mature Nramp1 polypeptide. The appearance of the Nramp1G169-encoded protein in transgenic macrophages was concomitant with the emergence of resistance to infection by M. bovis BCG, as measured by the extent of bacteria] replication in the spleen, and by S. typhimurium, as measured by survival after an intravenous challenge. The gain of function detected in transgenic Nramp1G169 animals establishes unambiguously that Nramp1 and Bcg/Ity/Lsh are allelic.
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对细胞内感染的天然抵抗力：Nramp1 编码易感 (Nramp1 D169) 小鼠品系的巨噬细胞中不存在的膜磷酸糖蛋白。
DOI：
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发表时间：
1996
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Vidal,SM;Pinner,E;Lepage,P;Gauthier,S;Gros,P
通讯作者：
Gros,P
DOI：
10.1073/pnas.92.22.10089
发表时间：
1995-10-24
影响因子：
11.1
作者：
CELLIER, M;PRIVE, G;GROS, P
通讯作者：
GROS, P
基因控制宿主对牛分枝杆菌（BCG）的抗性的细胞机制。
DOI：
--
发表时间：
1983
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Gros,P;Skamene,E;Forget,A
通讯作者：
Forget,A
基因控制的牛分枝杆菌 (BCG) 天然抗性的表型表达。
DOI：
--
发表时间：
1984
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Stach,JL;Gros,P;Forget,A;Skamene,E
通讯作者：
Skamene,E
Ity 基因座的主要作用是对相对免受杀死的鼠伤寒沙门氏菌的生长速率。
DOI：
--
发表时间：
1990
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
BenjaminJr,WH;Hall,P;Roberts,SJ;Briles,DE
通讯作者：
Briles,DE