1. ¹PhysioGenix Inc., Wauwatosa, WI, USA
2. ²Department of Physiology Medical College of Wisconsin, Milwaukee, WI, USA
3. ³Kidney Disease Center, Medical College of Wisconsin, Milwaukee, WI, USA
4. ⁴Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
5. ⁵Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, USA

Correspondence: Dr SH Nye, Research, PhysioGenix Inc., 10437 Innovation Drive, Milwaukee, WI 53226, USA. E-mail: snye@physiogenix.com

⁶Current address: Medical College of Wisconsin, Milwaukee, WI, USA

⁷Current address: Covance Laboratories Inc., Madison, WI, USA

Received 13 July 2006; Revised 3 February 2007; Accepted 16 February 2007; Published online 17 April 2007.

Abstract

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 g/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.