A locus on chromosome 1 promotes susceptibility of experimental autoimmune myocarditis and lymphocyte cell death

Abstract We previously identified by linkage analysis a region on chromosome 1 ( Eam1 ) that confers susceptibility to experimental autoimmune myocarditis (EAM). To evaluate the role of Eam1 , we created a congenic mouse strain, carrying the susceptible Eam1 locus of A.SW on the resistant B10.S back...

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Bibliographic Details
Published in:Clinical immunology (Orlando, Fla. Print) Fla. Print), 2009-01, Vol.130 (1), p.74-82
Main Authors: Ligons, Davinna L, Guler, Mehmet L, Li, Haiyan S, Rose, Noel R
Format: Article
Language:English
Subjects:
Allergy and Immunology
Animals
Apoptosis
Autoimmune
Autoimmune Diseases - genetics
Autoimmune Diseases - immunology
Autoimmune Diseases - metabolism
Biological and medical sciences
Cardiology. Vascular system
Caspase
Caspases - metabolism
Cell Death
Chromosome
Chromosomes, Mammalian - genetics
Enzyme Activation
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Gene
Genetic Predisposition to Disease - genetics
Heart
Immunization
Locus
Lymphocyte Activation - immunology
Lymphocytes - cytology
Lymphocytes - metabolism
Male
Medical sciences
Mice
Myocarditis
Myocarditis - genetics
Myocarditis - immunology
Myocarditis - metabolism
Myocarditis. Cardiomyopathies
Myosins - immunology
Regulation
Rodent
Susceptibility
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Summary:Abstract We previously identified by linkage analysis a region on chromosome 1 ( Eam1 ) that confers susceptibility to experimental autoimmune myocarditis (EAM). To evaluate the role of Eam1 , we created a congenic mouse strain, carrying the susceptible Eam1 locus of A.SW on the resistant B10.S background (B10.A- Eam1 congenic) and analyzed three outcomes: 1) the incidence and severity of EAM, 2) the susceptibility of lymph node cells (LNCs) to Cy-enhanced cell death, and 3) susceptibility of lymphoctyes to antigen-induced cell death. Incidence of myocarditis in B10.A- Eam1 congenic mice was comparable to A.SW mice, confirming that Eam1 plays an important role in disease development. Caspase 3, 8 and 9 activation in LNCs following Cy treatment and in CD4+ T cells after immunization with myosin/CFA was significantly lower in A.SW than B10.S mice whereas B10.A- Eam1 congenic mice exhibited an intermediate phenotype. Our results show that Eam1 reduces lymphocyte apoptosis and increases susceptibility to EAM.
ISSN:1521-6616
1521-7035
DOI:10.1016/j.clim.2008.06.015