Novel nonmajor histocompatibility complex-linked loci from mouse chromosome 17 confer susceptibility to viral-mediated chronic autoimmune myocarditis.
BACKGROUND
Development of viral-induced chronic myocarditis is thought to involve both environmental and genetic factors. However, to date, no susceptibility genes have been identified.


RESULTS
We sought to identify loci that confer susceptibility to viral-induced chronic myocarditis with the use of chromosome substitution strain mice that are composed of 1 chromosome from the disease susceptible A/J strain on an otherwise resistant C57BL/6 background. By this method, we identified chromosome 17 to confer susceptibility. To further isolate the region of susceptibility, 8 strains of mice congenic for different portions of chromosome 17 were generated. Characterization of these strains identified at least 4 susceptibility loci on the chromosome. Three of these loci are located in the proximal 22.8 cM, whereas the fourth locus is located in the portion of the chromosome distal to 34.3 cM.


CONCLUSIONS
We have identified 4 loci that confer susceptibility of viral-induced chronic myocarditis. Of these loci, 3 were distinct from the major histocompatibility complex locus and thus represent novel susceptibility loci. The close proximately of the 2 novel loci with susceptibility loci for other autoimmune diseases such as type 1 diabetes and chronic experimental autoimmune thyroiditis suggests the presence of global autoimmune susceptibility genes.
Poffenberger
Maya C
MC
The University of British Columbia, Vancouver, Canada.
Shanina
Iryna
I
Aw
Connie
C
El Wharry
Nahida
N
Straka
Nadine
N
Fang
Dianne
D
Baskin-Hill
Annie E
AE
Spiezio
Sabrina H
SH
Nadeau
Joseph H
JH
Horwitz
Marc S
MS
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000821:virology; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018895:Microsatellite Repeats; D009205:Myocarditis / Q000235:genetics / Q000276:immunology / Q000821:virology; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology / Q000821:virology; D055815:Young Adult