Two major interacting chromosome loci control disease susceptibility in murine model of spondyloarthropathy

A. Végvári, Z. Szabó, S. Szántó, Andrew B. Nesterovitch, Katalin Mikecz, Tibor T. Glant, Vyacheslav A. Adarichev

Research output: Contribution to journalArticle

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Abstract

Autoimmune spondylitis was induced in BALB/c mice and their MHC-matched (BALB/c × DBA/2)F1 and F2 hybrids by systemic immunization with cartilage/intervertebral disk proteoglycan (PG). As in human ankylosing spondylitis, the MHC was the major permissive genetic locus in murine PG-induced spondylitis (PGIS). Two major non-MHC chromosome loci with highly significant linkage were found on chromosomes 2 (Pgis2) and 18 (Pgis1) accounting for 40% of the entire F2 trait variance. The dominant spondylitis-susceptibility allele for Pgis2 locus is derived from the BALB/c strain, whereas the Pgis1 recessive allele was present in the disease-resistant DBA/2 strain. The Pgis1 locus significantly affected the disease-controlling Pgis2 locus, inducing as high incidence of spondylitis in F2 hybrids as was found in the spondylitis-susceptible parent BALB/c strain. Additional disease-controlling loci with suggestive linkage were mapped to the chromosomes 12, 15, and 19. Severity of spondylitis in F2 mice positively correlated with serum levels of amyloid A, IL-6, and Pg-specific Abs, and showed negative correlation with Ag-induced T cell proliferation, IFN-γ, IL-4, and TNF-α production. A major locus controlling serum IL-6 was found on chromosome 14 near osteoclast differentiation factor Tnfsf11. Locus on chromosome 11 near the Stat3 and Stat5 genes controlled serum level of the Ig IgG2a isotype. The two major genetic loci Pgis1 and Pgis2 of murine spondylitis were homologous to chromosome regions in human genome, which control ankylosing spondylitis in human patients. Thus, this animal model of experimentally induced spondylitis might facilitate the identification of spondylitis-susceptibility genes in humans.

Original languageEnglish
Pages (from-to)2475-2483
Number of pages9
JournalJournal of Immunology
Volume175
Issue number4
Publication statusPublished - Aug 15 2005

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Spondylitis
Spondylarthropathies
Internal-External Control
Disease Susceptibility
Chromosomes
Genetic Loci
Ankylosing Spondylitis
Proteoglycans
Interleukin-6
Serum
Alleles
RANK Ligand
Chromosomes, Human, Pair 19
Chromosomes, Human, Pair 18
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 14
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 2
Intervertebral Disc

ASJC Scopus subject areas

  • Immunology

Cite this

Two major interacting chromosome loci control disease susceptibility in murine model of spondyloarthropathy. / Végvári, A.; Szabó, Z.; Szántó, S.; Nesterovitch, Andrew B.; Mikecz, Katalin; Glant, Tibor T.; Adarichev, Vyacheslav A.

In: Journal of Immunology, Vol. 175, No. 4, 15.08.2005, p. 2475-2483.

Research output: Contribution to journalArticle

Végvári, A. ; Szabó, Z. ; Szántó, S. ; Nesterovitch, Andrew B. ; Mikecz, Katalin ; Glant, Tibor T. ; Adarichev, Vyacheslav A. / Two major interacting chromosome loci control disease susceptibility in murine model of spondyloarthropathy. In: Journal of Immunology. 2005 ; Vol. 175, No. 4. pp. 2475-2483.
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AU - Mikecz, Katalin

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