Evidence indicates that environmental factors play a major role in precipitating systemic autoimmunity in genetically susceptible individuals, however, little is known about the mechanisms involved. Certain heavy metals, such as mercury, are potent environmental immunostimulants that produce a number of immunopathologic sequelae, including lymphadenopathy, hypergammaglobulinemia, and even overt systemic autoimmunity. Studies in mice indicate that susceptibility to such metal induced immunopathology is influenced by both MHC and non MHC genes.
The aims of this proposal are to define the genetic factors required for mercury induced autoimmunity in a well characterized animal model. Genetic studies will identify loci conferring susceptibility or resistance to mercury induced autoimmunity using F2 intercrosses of SJL/J (susceptible) and DBA/2 (resistant) strains by linkage analysis of mercury induced immunopathologic features to a panel of microsatellite markers spanning the mouse genome. Congenic mice will be generated to define the role of these loci and the corresponding genes will be identified by several approaches. Identification of susceptibility/resistance genes and mechanisms relevant to the immunopathogenesis of mercury induced autoimmunity should provide important insights on the pathogenesis of autoimmunity, and may identify potential targets for intervention.
| Pollard, Kenneth M; Hultman, Per; Toomey, Christopher B et al. (2011) ?2-microglobulin is required for the full expression of xenobiotic-induced systemic autoimmunity. J Immunotoxicol 8:228-37 |
| Pollard, K Michael; Hultman, Per; Kono, Dwight H (2010) Toxicology of autoimmune diseases. Chem Res Toxicol 23:455-66 |
| Hultman, P; Taylor, A; Yang, J M et al. (2006) The effect of xenobiotic exposure on spontaneous autoimmunity in (SWR x SJL)F1 hybrid mice. J Toxicol Environ Health A 69:505-23 |
| Kono, Dwight H; Theofilopoulos, Argyrios N (2006) Genetics of SLE in mice. Springer Semin Immunopathol 28:83-96 |
| Pollard, K Michael; Hultman, Per; Kono, Dwight H (2005) Immunology and genetics of induced systemic autoimmunity. Autoimmun Rev 4:282-8 |
| Pollard, K Michael; Arnush, Marc; Hultman, Per et al. (2004) Costimulation requirements of induced murine systemic autoimmune disease. J Immunol 173:5880-7 |
| Kono, Dwight H; Park, Miyo S; Theofilopoulos, Argyrios N (2003) Genetic complementation in female (BXSB x NZW)F2 mice. J Immunol 171:6442-7 |
| Pollard, K Michael; Hultman, Per; Kono, Dwight H (2003) Using single-gene deletions to identify checkpoints in the progression of systemic autoimmunity. Ann N Y Acad Sci 987:236-9 |
| Theofilopoulos, A N; Kono, D H (2002) A genetic analysis of lupus. Allergy 57 Suppl 72:67-74 |
| Pollard, K M; Pearson, D L; Hultman, P et al. (2001) Xenobiotic acceleration of idiopathic systemic autoimmunity in lupus-prone bxsb mice. Environ Health Perspect 109:27-33 |
Showing the most recent 10 out of 14 publications
