Identification of the Gasa3 and Gasa4 autoimmune gastritis susceptibility genes using congenic mice and partitioned, segregative and interaction analyses

BALB/c mice thymectomized on their third day of life develop a high incidence of experimental autoimmune gastritis (EAG) which closely resembles human chronic atrophic (type A, autoimmune) gastritis. Linkage analysis of (BALB/cCrSlcxC57BL/6)F2 mice previously demonstrated that the Gasa1 and Gasa2 ge...

Full description

Saved in:
Bibliographic Details
Published in:Immunogenetics (New York) 2001-12, Vol.53 (9), p.741-750
Main Authors: Silveira, P A, Wilson, W E, Esteban, L M, Jordan, M A, Hawke, C G, van Driel, I R, Baxter, A G
Format: Article
Language:English
Subjects:
Animals
Autoimmune Diseases - genetics
Autoimmune Diseases - immunology
Breeding
chromosome 4
Chromosome Mapping
Gasa2 gene
Gasa3 gene
Gasa4 gene
Gastritis - genetics
Gastritis - immunology
Genes, Dominant
Genes, Recessive
Genetic Linkage
H-2 Antigens - genetics
Immunogenetics
Major Histocompatibility Complex
Mice
Mice, Congenic
Mice, Inbred BALB C
Mice, Inbred C57BL
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:BALB/c mice thymectomized on their third day of life develop a high incidence of experimental autoimmune gastritis (EAG) which closely resembles human chronic atrophic (type A, autoimmune) gastritis. Linkage analysis of (BALB/cCrSlcxC57BL/6)F2 mice previously demonstrated that the Gasa1 and Gasa2 genes on distal Chromosome (Chr) 4 have major effects on the development of EAG in this murine model, while other loci displayed a trend towards linkage. Here, we implemented partitioned chi(2)-analysis in order to develop a better understanding of the genotypes contributing to susceptibility and resistance at each linkage region. This approach revealed that linkage of Gasa1 and Gasa2 to EAG was due to codominant and recessive BALB/cCrSlc alleles, respectively. To identify additional EAG susceptibility genes, separate linkage studies were performed on Gasa1 heterozygotes and Gasa2 C57BL/6 homozygotes plus heterozygotes so as to minimize the effects of these disease genes. The enhanced sensitivity of these analyses confirmed the existence of a third EAG susceptibility gene (designated Gasa3) on Chr 6. Epistatic interactions between the Gasa2 EAG susceptibility gene and the H2 were also identified, and the presence of an H2-linked susceptibility gene (Gasa4) confirmed by analysis of H2 congenic mice.
ISSN:0093-7711
1432-1211
DOI:10.1007/s00251-001-0391-y