Pathogenetic role of an autoimmune susceptibility locus derived from MRL/MpJ strain chromosome 1 in chronic pancreas inflammation.
We examined the role of Mag, an autoimmune susceptibility locus encoded by the telomeric region of MRL/MpJ mouse chromosome 1, in the pathogenesis of autoimmune exocrinopathy. At nine to 12 months of age, strain-specific differences were observed in the pancreas of the animals. B- and T-cell-containing periductal/perivascular cell infiltrations in the pancreases of MRL/MpJ and B6.MRLc1 congenic C57BL/6-background Mag-carrying strains were more severe than were those of C57BL/6. Pancreatic periductal/perivascular cell infiltration was observed frequently in A/J, AKR/N, B6.MRLc1, C57BL/6, and MRL/MpJ, moderately in DBA/1 and DBA/2, and rarely in BALB/c and C3H/He strains. Females tended to have greater pancreatic periductal/perivascular cell infiltration than males. C57BL/6 mice possessed defined borders between cell infiltrations and acini, but borders were indistinct in MRL/MpJ and B6.MRLc1 mice. We attributed this to the invasion of inflammatory cells between each acinus and the disruption of acinar cells around cell infiltrations in the latter strains. No strain-specific differences were observed in the appearance of fibrotic lesions and high endothelial venules in the cell infiltrates. The levels of serum anti-dsDNA antibodies and amylase, and mRNA expression of tumor necrosis factor-α and Fc gamma receptor III (encoded on Mag) in the pancreases, were elevated in MRL/MpJ- and B6.MRLc1-strain mice relative to C57BL/6. These results emphasized the crucial roles of Mag in the molecular and genetic pathogenesis of autoimmune-mediated pancreatitis.
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Y
Y
Okada
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories, Chitose, Japan.
T
T
Nakamura
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
O
O
Ichii
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
S
S
Otsuka
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan y-kon@vetmed.hokudai.ac.jp.
Y
Y
Kon
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004247:DNA / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D019463:Mice, Inbred MRL lpr; D010195:Pancreatitis / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics; D012737:Sex Factors; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D012333:RNA, Messenger; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D004247:DNA
MRL/MpJ mouse; Telomeric region of chromosome 1; inflammatory exocrinopathy; pancreas