Nye S H, Wittenburg A L, Evans D L, O'Connor J A, Roman R J, Jacob H J
PhysioGenix Inc., 10437 Innovation Drive, Milwaukee, WI 53226, USA.
Pharmacogenomics J. 2008 Feb;8(1):16-22. doi: 10.1038/sj.tpj.6500448. Epub 2007 Apr 17.
We examined whether survival of different rat strains administered anthrax lethal toxin is genetically determined. A reproducible test population of first filial generation hybrid rats was bred based on the susceptibility of progenitors to anthrax lethal toxin and to maximize genetic diversity across the strains. These rats were then tested with varying doses of anthrax lethal toxin. We found that all 'sensitive' strains died within 2 h following systemic administration of 240 mug/kg lethal toxin, while one strain survived following a five times higher dose (1.4 mg/kg). The ability of lethal toxin to lyse macrophage cultures derived from the bone marrow of these strains corresponded with in vivo results. We conclude that a rat test population can detect strain differences in response to anthrax lethal toxin. Survival is influenced by the host genome background and is likely due to a single gene with a recessive mode of inheritance.
我们研究了给予炭疽致死毒素后不同品系大鼠的存活情况是否由基因决定。基于亲代对炭疽致死毒素的易感性并为使各品系间的遗传多样性最大化，培育了具有可重复性的第一代杂交大鼠测试群体。然后用不同剂量的炭疽致死毒素对这些大鼠进行测试。我们发现，所有“敏感”品系在全身给予240微克/千克致死毒素后2小时内死亡，而一个品系在五倍高剂量（1.4毫克/千克）下存活。致死毒素对源自这些品系骨髓的巨噬细胞培养物的裂解能力与体内结果相符。我们得出结论，大鼠测试群体能够检测出对炭疽致死毒素反应的品系差异。存活受宿主基因组背景影响，可能归因于一个具有隐性遗传模式的单基因。
