Two genetic loci independently confer susceptibility to autoimmune gastritis.
Autoimmune gastritis is a CD4+ T cell-mediated disease induced in genetically susceptible mice by thymectomy on the third day after birth. Previous linkage analysis indicated that Gasa1 and Gasa2, the major susceptibility loci for gastritis, are located on mouse chromosome 4. Here we verified these linkage data by showing that BALB.B6 congenic mice, in which the distal approximately 40 Mb of chromosome 4 was replaced by C57BL/6 DNA, were resistant to autoimmune gastritis. Analysis of further BALB.B6 congenic strains demonstrated that Gasa1 and Gasa2 can act independently to cause full expression of susceptibility to autoimmune disease. Gasa1 and Gasa2 are located between D4Mit352-D4Mit204 and D4Mit343-telomere, respectively. Numerical differences in Foxp3+ regulatory T cells were apparent between the BALB/c and congenic strains, but it is unlikely that this phenotype accounted for differences in autoimmune susceptibility. The positions of Gasa1 and Gasa2 correspond closely to the positions of Idd11 and Idd9, two autoimmune diabetes susceptibility loci in nonobese diabetic (NOD), mice and this prompted us to examine autoimmune gastritis in NOD mice. After neonatal thymectomy, NOD mice developed autoimmune gastritis, albeit at a slightly lower incidence and severity of disease than in BALB/c mice. Diabetes-resistant congenic NOD.B6 mice, harbouring a B6-derived interval encompassing the Gasa1/2-Idd9/11 loci, demonstrated a slight reduction in the incidence of autoimmune gastritis. This reduction was not significant compared with the reduction observed in BALB.B6 congenic mice, suggesting a difference in the genetic aetiology of autoimmune gastritis in NOD and BALB mice.
Ang
Desmond K Y
DK
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC 3010, Australia.
Brodnicki
Thomas C
TC
Jordan
Margaret A
MA
Wilson
Wendy E
WE
Silveira
Pablo
P
Gliddon
Briony L
BL
Baxter
Alan G
AG
van Driel
Ian R
IR
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology* / Q000601:surgery; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D005756:Gastritis / Q000235:genetics* / Q000276:immunology* / Q000601:surgery; D005799:Genes, Dominant; D008040:Genetic Linkage / Q000235:genetics* / Q000276:immunology; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013934:Thymectomy