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

Authors
Journal
Clinical Immunology
1521-6616
Publisher
Elsevier
Publication Date
Volume
130
Issue
1
Identifiers
DOI: 10.1016/j.clim.2008.06.015
Keywords
  • Autoimmune
  • Apoptosis
  • Gene
  • Regulation
  • Rodent
  • Caspase
  • Susceptibility
  • Myocarditis
  • Chromosome
  • Locus
Disciplines
  • Medicine

Abstract

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.

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