Exclusion of Kif1c as a candidate gene for anthrax toxin susceptibility

Different strains of mice possess varying degrees of susceptibility to anthrax lethal toxin (LT). Previous studies have suggested a responsible locus Ltxs1 that contains 10 or more known genes, but functional relevance has been reported for two genes, Kif1c and Nalp1b. In this study, we attempted to determine the involvement of Kif1c in anthrax susceptibility using Kif1c knockout mice. We established Kif1c knockout mice with LT-sensitive 129/Sv-derived embryonic stem cells followed by 13 backcrosses with LT-resistant C57BL/6J mice (B6) to be congenic. These knockout mice and their primary macrophages showed significantly higher sensitivity to LT than wild-type B6. However, when we replaced the remaining 129/Sv genome adjacent to the targeted Kif1c locus with the B6 genome, this sensitivity was lost. This suggested that the sensitivity to LT in the originally established Kif1c knockout mice was not due to the loss of the Kif1c gene, but was because of the presence of the 129/Sv-derived genes adjacent to the disrupted Kif1c locus. Thus, Kif1c was excluded as a candidate anthrax susceptibility gene.