NATURAL-RESISTANCE TO INFECTION WITH LEGIONELLA-PNEUMOPHILA - CHROMOSOMAL LOCALIZATION OF THE LGN1 SUSCEPTIBILITY GENE
NATURAL-RESISTANCE TO INFECTION WITH LEGIONELLA-PNEUMOPHILA - CHROMOSOMAL LOCALIZATION OF THE LGN1 SUSCEPTIBILITY GENE
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DOI：
10.1007/bf00356173
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发表时间：
1995-08-01
期刊：
影响因子：
2.5
通讯作者：
GROS, P
中科院分区：
文献类型：
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作者：
BECKERS, MC;YOSHIDA, S;GROS, P
嗜肺军团菌是一种严格的细胞内病原体，在人类和豚鼠宿主的专业吞噬细胞中复制。尽管来自大多数近交株的小鼠巨噬细胞不允许嗜肺军团菌在细胞内复制，但来自小鼠品系A/J的炎性巨噬细胞完全允许该细菌在细胞内复制。这种遗传差异是由名为 Lgn1 的单个常染色体基因的表达控制的，非宽容性表现得完全优于宽容性。我们总共使用了 25 个 AXB/BXA 重组近交系小鼠品系和 182 个 (A/J x C57BL/6J) x A/J 分离回交后代（A/J，允许；C57BL/6J，非允许）来定位 Lgn1 基因。通过用嗜肺军团菌体外感染炎性巨噬细胞，对动物进行单独分型，以确定其对细胞内复制的耐受性。所有动物被分成两个不重叠的组。对 AXB/BXA 菌株的 Lgn1 菌株分布模式的检查最初确定了与染色体 (Chr) 13 标记的连锁。对 25 个 AXB/BXA 品系和 182 个回交后代进行 II Chr 13 标记的基因分型，确定 Lgn1 映射到 Chr 13，基因顺序和基因间距离为 D13Mit231-(5.5 +/- 1.5)-D13Mit193-(2.2 +/- 0.9)-D13Mit194-(1.1 +/- 0.6)D13Mit128-(2.6+/-1.0)-Lgn1-(2.2+/-0.9)-D13Mit70-(3.9+/-1.3)-D13Mit73-(7.2+/-1.7)-D13Mit53-(0.7+/-0.5)-D13Mit32-(0.7+/- 0.5)-D13Mit77-(0.7+/-0.5)-D13Mit78。 Chr 13 的这一部分与人 Chr 5 的远端部分 5q11-5q13 同源，表明人 LGN1 同源物的可能位置。了解 A/J 巨噬细胞对嗜肺军团菌高度许可的分子基础可能有助于了解该细菌在高度许可的人类吞噬细胞中的生存策略。这可以通过 Lgn1 的定位克隆来实现，本文报道的 Lgn1 亚染色体区域的鉴定是实现该目标的第一步。
Legionella pneumophila is a strict intracellular pathogen that replicates in the professional phagocytes of the human and guinea pig host. Although murine macrophages from most inbred strains are non-permissive to intracellular replication of L. pneumophila, inflammatory macrophages from the mouse strain A/J are completely permissive to intracellular replication of this bacterium. This genetic difference is controlled by the expression of a single autosomal gene designated Lgn1, with non-permissiveness behaving as completely dominant over permissiveness. We have used a total of 25 AXB/BXA recombinant inbred mouse strains and 182 (A/J x C57BL/6J) x A/J segregating backcross progeny (A/J, permissive; C57BL/6J, non-permissive) to map the Lgn1 gene. Animals were individually typed for tolerance to intracellular replication by in vitro infection of their inflammatory macrophages with L. pneumophila. All animals segregated into two nonoverlapping groups. Examination of the strain distribution pattern of the AXB/BXA strains for Lgn1 initially identified linkage to Chromosome (Chr) 13 markers. Genotyping of the 25 AXB/BXA strains and the 182 backcross progeny for II Chr 13 markers established that Lgn1 mapped to Chr 13, with the gene order and intergene distance D13Mit231-(5.5 +/- 1.5)-D13Mit193-(2.2 +/- 0.9)-D13Mit194-(1.1 +/- 0.6)D13Mit128-(2.6 +/- 1.0)-Lgn1-(2.2 +/- 0.9)-D13Mit70-(3.9 +/- 1.3)-D13Mit73-(7.2 +/- 1.7)-D13Mit53-(0.7 +/- 0.5)-D13Mit32-(0.7 +/- 0.5)-D13Mit77-(0.7 +/- 0.5)-D13Mit78. This portion of Chr 13 is homologous to the distal portion of human Chr 5, 5q11-5q13, suggesting a possible location of a human LGN1 homolog. Understanding the molecular basis of the high permissiveness of A/J macrophage to L. pneumophila may shed light on the survival strategy of this bacterium in highly permissive human phagocytes. This may be achieved by positional cloning of Lgn1, and the identification of the Lgn1 subchromosomal region reported here is a first step towards that goal.