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| Ltx1, a mouse locus that influences the susceptibility of macrophages to cytolysis caused by intoxication with Bacillus anthracis lethal factor, maps to chromosome 11 |
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| Author(s): Roberts JE, Watters JW, Ballard JD, Dietrich WF |
| Source: MOLECULAR MICROBIOLOGY Volume: 29 Issue: 2 Pages: 581-591 Published: JUL 1998 |
| Times Cited: 52 References: 38 |
| Abstract: The lethal factor (LF) toxin that is produced by Bacillus anthracis plays an important role in the pathogenesis of anthrax. LF has mononuclear phagocyte-specific intoxicating effects that are not well understood. We have identified genetic differences in inbred mouse strains that determine whether their cultured macrophages are susceptible to the cytolytic effect of LF intoxication. Our identification of resistant and susceptible mouse strains enabled us to analyse crosses between these strains and to map a single responsible gene (called Ltx1) to chromosome 11, Ltx1 probably influences intoxication events that occur after the delivery of LF to the cytosol, as all mouse macrophages are killed by polypeptides containing the catalytic domain of Diphtheria toxin fused to the domain of LF required for cytosolic transport. Furthermore, the susceptibility phenotype is dominant to resistance, suggesting that resistance is caused by an absence of or polymorphism in a molecule that acts jointly with, or downstream of, the activity of LF, Our mapping of Ltx1 is a crucial first step in its positional cloning, which will provide more information about the mechanism of LF intoxication. |
| Document Type: Article |
| Language: English |
| Reprint Address: Dietrich, WF (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, 200 Longwood Ave, Boston, MA 02115 USA |
Addresses:
1. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
2. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
3. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA |
| Publisher: BLACKWELL SCIENCE LTD, P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND |
| Subject Category: Biochemistry & Molecular Biology; Microbiology |
| IDS Number: 113PM |
| ISSN: 0950-382X |
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