Richardson S H, Sexton T, Rader J, Kajs C
Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157.
Clin Infect Dis. 1993 Mar;16 Suppl 2:S83-91. doi: 10.1093/clinids/16.supplement_2.s83.
Evidence has been accumulating that humans are genetically predisposed to cholera gravis. Using the sealed adult mouse model, we found that certain inbred mice were also hypersensitive to cholera toxin (CT). Such mice were designated ETS+ (enterotoxin sensitive), and the trait was linked to the K end of the mouse H-2 histocompatibility complex. Cells isolated from ETS+ mice bound more CT and accumulated more cyclic adenosine monophosphate (cAMP) after intoxication. Analysis of ETS+ cells showed that they express lesser amounts of the non-GM1 gangliosides that block or compete for relevant CT binding sites in ETS- cells. Conversion of ETS- non-GM1 gangliosides to GM1 with neuraminidase increased CT binding and cAMP responses. Reconstitution of nonreactive ganglioside-deficient cells with ETS+ or ETS- gangliosides caused them to bind CT like the original ETS+ or ETS- cells. Ganglioside expression genes known to map to the same H-2-linked region as the ETS phenotype seem to be involved in controlling murine susceptibility to CT.
越来越多的证据表明，人类在基因上易患重症霍乱。利用成年封闭小鼠模型，我们发现某些近交系小鼠对霍乱毒素（CT）也高度敏感。此类小鼠被指定为ETS+（肠毒素敏感型），该性状与小鼠H-2组织相容性复合体的K端相关。从ETS+小鼠分离出的细胞在中毒后结合了更多的CT，并积累了更多的环磷酸腺苷（cAMP）。对ETS+细胞的分析表明，它们表达的非GM1神经节苷脂较少，而这些神经节苷脂会阻断或竞争ETS-细胞中的相关CT结合位点。用神经氨酸酶将ETS-非GM1神经节苷脂转化为GM1会增加CT结合和cAMP反应。用ETS+或ETS-神经节苷脂重建无反应性的神经节苷脂缺陷细胞，会使它们像原始的ETS+或ETS-细胞一样结合CT。已知定位于与ETS表型相同的H-2连锁区域的神经节苷脂表达基因似乎参与控制小鼠对CT的易感性。
