Rat survival to anthrax lethal toxin is likely controlled by a single gene.
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.
Nye
S H
SH
PhysioGenix Inc., 10437 Innovation Drive, Milwaukee, WI 53226, USA. snye@physiogenix.com
Wittenburg
A L
AL
Evans
D L
DL
O'Connor
J A
JA
Roman
R J
RJ
Jacob
H J
HJ
D000818:Animals; D000942:Antigens, Bacterial / Q000633:toxicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D001947:Breeding; D002469:Cell Separation; D002478:Cells, Cultured; D004351:Drug Resistance; D016678:Genome; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY; D013045:Species Specificity; D016019:Survival Analysis
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin