Vms1^A/J
QTL Variant Detail

Summary

• QTL variant: Vms1^A/J
• Name: viral myocarditis susceptibility locus 1; A/J
• MGI ID: MGI:3712475
• QTL: Vms1 Location: unknown Genetic Position: Chr3, Syntenic

Variant origin

• Strain of Specimen: A/J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers susceptibility to coxsackievirus B3-induced myocarditis compared to C57BL/10Snsg. This allele also confers susceptibility to coxsackievirus B3-induced sarcolemma damage in females compared to C57BL/10SnSg. (J:121574)

Notes

71% of F2 animals homozygous for this allele exhibit myocarditis.

Mapping and Phenotype information for this QTL, its variants and associated markers

J:121574

Linkage analysis was performed on 384 (A/J x B10.A-H2^a H2-T18^a/SgSnJ)F2 mice to identify QTLs associated with host susceptibility to coxsackievirus B3 (CVB3)- induced myocarditis. Genome scan utilized 146 polymorphic markers at a 10 cM resolution. Parental strain A/J is susceptible displaying severe and extensive myocyte necrosis 8 days post-infection whereas parental strain B10.A-H2^a H2-T18^a/SgSnJ is relatively resistant, with males having higher susceptible than females. Myocarditis phenotypes were assessed by myocarditis severity score and sarcolemma disruption.

Linkage to CVB3-induced myocarditis was detected and confirmed at 86.7 cM on mouse Chromosome 3 near D3Mit19 (LOD=4.7; P=0.0046). This locus is named Vms1 (viral myocarditis susceptibility locus 1). The 1.5 LOD support interval spans a 16 cM distance. Vms1 also shows significant linkage to sarcolemma disruption in females only with P=0.00148 at D3Mit128 (83.5 cM). A/J derived alleles at Vms1 confer susceptibility to myocarditis (71% of A/J homozygous F2 mice) and sarcolemma disruptions (in females). Hrtfm2 (76.2 cM) is a previously identified heart failure QTL mapping near Vms1. Candidate genes for Vms1 include Tnni3k, If1 (87.7 cM), and Ifi44.

Linkage to sarcolemma disruption in males was detected and confirmed at 80 cM on mouse Chromosome 1 near D1Mit200 (P=0.00005). This locus is named Vms2 (viral myocarditis susceptibility locus 2). The 1.5 LOD support interval for Vms2 spans a 40 cM distance. C57BL/10SnSg-derived alleles at Vms2 conferincreased sarcolemma damage in male mice. Ity3 (71.5 cM), Sle1 (103 cM), Lbw7 (90 cM), Nba2 (95 cM), Yaa4 (aka Bxs3, 100 cM), and Mancq1 (63.1 cM) are immune-related QTLs mapping near this interval. Ptprc (aka CD45, 74 cM), Daf2 (67.6 cM), and Tnnt2 (60 cM) are potential candidate genes for Vms2.

Vms3 (viral myocarditis susceptibility locus 3) mapped to 38 cM on mouse Chromosome 4 near D4Mit81 (P=0.0022). The 1.5 LOD support interval spans 7 cM. C57BL/10SgSn-derived alleles at Vms3 confer increased sarcolemma damage in male mice. Potential candidate genes for Vms3 include the interferon alpha gene cluster (Ifna) at 42.6 cM.

References

• Original: J:121574 Aly M, et al., Complex genetic control of host susceptibility to coxsackievirus B3-induced myocarditis. Genes Immun. 2007 Apr;8(3):193-204
• All: 1 reference(s)