Genetic analysis of the influence of pertussis toxin on experimental allergic encephalomyelitis susceptibility: An environmental agent can override genetic checkpoints

Pertussis toxin (PTX) is a potent ancillary adjuvant used to elicit several different autoimmune diseases, including experimental allergic encephalomy elitis (EAE), To delineate the genetics of PTX effect in EAE, Ive mapped EA E-modifying (eae-m) loci in cohorts of backcross mice immunized with and wi thout PTX, In this study, we analyzed the genetic basis of EAE Susceptibili ty and severity and the intermediate phenotypes of mononuclear cell infiltr ation, suppuration, and demyelination, In animals immunized with PTX, one m ajor locus, eae9, controls disease susceptibility and severity. Eae9 also r egulates the extent of mononuclear cell infiltration of the spinal cord in male mice. Without PTX, five eae-m loci mere noted, including three new loc i in intervals on chromosomes 8 (eae14), 10 (eae17), and 18 (eae18), Taken together, these results suggest that eae9 controls the effects of PTX in EA E susceptibility, and is capable of overriding the other genetic checkpoint s in the pathogenesis of this disease.