Richardson S H, Kuhn R E
Infect Immun. 1986 Nov;54(2):522-8. doi: 10.1128/iai.54.2.522-528.1986.
A sealed adult mouse (SAM) model was developed for studies on the effects of cholera enterotoxin (CT). With this system, 38 strains of outbred, inbred, congenic, recombinant, and mutant mice were starved for 24 h, anorectally occluded with cyanoacrylamide ester glue, given CT per os, and sacrificed at 6 h. Fluid accumulation (FA) values were calculated as gut weight to body weight ratios. At a saturating dose of CT (24 micrograms per mouse), FA responses were found to be independent of body weight and gut length. It was found, using recombinant and congenic mice, that mice which possess the H-2k haplotype (homozygous or heterozygous) are 2.5 to 3 times less responsive to CT than animals with the H-2b haplotype. The allele(s) responsible for this affect is located near the K end of the H-2 complex. Inbred and congenic mice given CT intravenously exhibited the same (b = responder, k = nonresponder) pattern in terms of weight loss and death, thus indicating that the H-2 effect is not limited just to the small intestinal epithelium. Mice given sublethal doses of CT intravenously and challenged after conversion to SAM 14 days later showed an immune response inversely related to weight loss (i.e., b haplotypes lost 10 to 15% body weight, recovered, but were not protected against challenge; k haplotypes lost little or no weight but were protected). To examine the possibility of a cellular basis for control of innate responses to CT, responder C57BL/10 (B10) mice were irradiated with 950 rads and immediately reconstituted with bone marrow from (B10 X B10.BR)F1 (nonresponder) mice. The chimeras became nonresponsive to CT when challenged 5 weeks after reconstitution. Reconstituted B10 controls responded normally. Outbred and inbred nude athymic mice also were nonresponsive when compared with normal responder controls. These data demonstrate a genetic basis for resistance to CT and that response and nonresponse is mediated, at least in part, by cells derived from bone marrow.
为了研究霍乱肠毒素（CT）的作用，建立了一种成年封闭小鼠（SAM）模型。利用该系统，对38种远交、近交、同源、重组和突变小鼠品系进行24小时饥饿处理，用氰基丙烯酸酯胶进行肛门直肠封闭，经口给予CT，并在6小时后处死。液体蓄积（FA）值以肠重与体重之比计算。在CT饱和剂量（每只小鼠24微克）下，发现FA反应与体重和肠长度无关。利用重组和同源小鼠发现，具有H-2k单倍型（纯合或杂合）的小鼠对CT的反应比具有H-2b单倍型的动物低2.5至3倍。负责这种影响的等位基因位于H-2复合体的K端附近。静脉注射CT的近交和同源小鼠在体重减轻和死亡方面表现出相同的模式（b = 反应者，k = 无反应者），因此表明H-2效应不仅限于小肠上皮。静脉注射亚致死剂量CT并在14天后转化为SAM后受到攻击的小鼠显示出与体重减轻呈负相关的免疫反应（即，b单倍型体重减轻10%至15%，恢复但未受到攻击保护；k单倍型体重减轻很少或没有减轻但受到保护）。为了研究对CT先天反应控制的细胞基础的可能性，对反应性C57BL/10（B10）小鼠进行950拉德照射，并立即用（B10×B10.BR）F1（无反应者）小鼠的骨髓进行重建。嵌合体在重建5周后受到攻击时对CT变得无反应。重建的B10对照正常反应。与正常反应对照相比，远交和近交裸胸腺小鼠也无反应。这些数据证明了对CT抗性存在遗传基础，并且反应和无反应至少部分由源自骨髓的细胞介导。
