Journal
JOURNAL OF IMMUNOLOGY
Volume 164, Issue 6, Pages 3420-3425Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.164.6.3420
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Funding
- NIAID NIH HHS [AI41747] Funding Source: Medline
- NINDS NIH HHS [NS36526, NS25519] Funding Source: Medline
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Pertussis toxin (PTX) is a potent ancillary adjuvant used to elicit several different autoimmune diseases, including experimental allergic encephalomyelitis (EAE), To delineate the genetics of PTX effect in EAE, Ive mapped EAE-modifying (eae-m) loci in cohorts of backcross mice immunized with and without PTX, In this study, we analyzed the genetic basis of EAE Susceptibility and severity and the intermediate phenotypes of mononuclear cell infiltration, suppuration, and demyelination, In animals immunized with PTX, one major locus, eae9, controls disease susceptibility and severity. Eae9 also regulates the extent of mononuclear cell infiltration of the spinal cord in male mice. Without PTX, five eae-m loci mere noted, including three new loci in intervals on chromosomes 8 (eae14), 10 (eae17), and 18 (eae18), Taken together, these results suggest that eae9 controls the effects of PTX in EAE susceptibility, and is capable of overriding the other genetic checkpoints in the pathogenesis of this disease.
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