Medical College of Wisconsin
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Rat survival to anthrax lethal toxin is likely controlled by a single gene. Pharmacogenomics J 2008 Feb;8(1):16-22

Date

04/19/2007

Pubmed ID

17440430

DOI

10.1038/sj.tpj.6500448

Scopus ID

2-s2.0-38349177167 (requires institutional sign-in at Scopus site)   19 Citations

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 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.

Author List

Nye SH, Wittenburg AL, Evans DL, O'Connor JA, Roman RJ, Jacob HJ



MESH terms used to index this publication - Major topics in bold

Animals
Antigens, Bacterial
Bacterial Toxins
Breeding
Cell Separation
Cells, Cultured
Drug Resistance
Genome
Macrophages
Male
Rats
Rats, Inbred F344
Rats, Inbred Lew
Rats, Inbred WKY
Species Specificity
Survival Analysis