susceptibility to anthrax lethal toxin-induced rat death is controlled by a single chromosome 10 locus that includes rnlrp1对炭疽致命toxin-induced老鼠死亡是由单个染色体10轨迹控制,包括rnlrp1.pdf

Susceptibility to Anthrax Lethal Toxin-Induced Rat Death Is Controlled by a Single Chromosome 10 Locus That Includes rNlrp1 1 2 1 1 2 Zachary L. Newman , Morton P. Printz , Shihui Liu , Devorah Crown , Laura Breen , Sharmina Miller- 1 3 1 1 Randolph , Pamela Flodman , Stephen H. Leppla , Mahtab Moayeri * 1 National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Department of Pharmacology, University of California-San Diego, La Jolla, California, United States of America, 3 Department of Pediatrics, University of California, Irvine, Irvine, California, United States of America Abstract Anthrax lethal toxin (LT) is a bipartite protease-containing toxin and a key virulence determinant of Bacillus anthracis. In mice, LT causes the rapid lysis of macrophages isolated from certain inbred strains, but the correlation between murine macrophage sensitivity and mouse strain susceptibility to toxin challenge is poor. In rats, LT induces a rapid death in as little as 37 minutes through unknown mechanisms. We used a recombinant inbred (RI) rat panel of 19 strains generated from LT- sensitive and LT-resistant progenitors to map LT sensitivity in rats to a locus on chromosome 10 that includes the inflammasome NOD-like receptor (NLR) sensor, Nlrp1. This gene is the closest rat homolog of mouse Nlrp1b, which was previously shown to control murine macrophage sensitivity to LT. An absolute correlation between in vitro macrophage sensitivity to LT-induced lysis and animal susceptibility to the toxin was found for the 19 RI strains and 12 additional rat