Disease-promoting and-protective genomic loci on mouse chromosomes 3 and 19 control the incidence and severity of autoimmune arthritis

T. T. Glant, V. A. Adarichev, F. Boldizsar, T. Besenyei, A. Laszlo, K. Mikecz, T. A. Rauch

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Proteoglycan (PG)-induced arthritis (PGIA) is a murine model of rheumatoid arthritis. Arthritis-prone BALB/c mice are 100% susceptible, whereas the major histocompatibility complex-matched DBA/2 strain is completely resistant to PGIA. To reduce the size of the disease-suppressive loci for sequencing and to find causative genes of arthritis, we created a set of BALB/c.DBA/2-congenic/ subcongenic strains carrying DBA/2 genomic intervals overlapping the entire Pgia26 locus on chromosome 3 (chr3) and Pgia23/Pgia12 loci on chr19 in the arthritis-susceptible BALB/c background. Upon immunization of these subcongenic strains and their wild-type (BALB/c) littermates, we identified a major Pgia26a sublocus on chr3 that suppressed disease onset, incidence and severity via controlling the complex trait of T-cell responses. The region was reduced to 3 Mbp (11.8 Mbp with flanking regions) in size and contained gene(s) influencing the production of a number of proinflammatory cytokines. Additionally, two independent loci (Pgia26b and Pgia26c) suppressed the clinical scores of arthritis. The Pgia23 locus (∼ 3 Mbp in size) on chr19 reduced arthritis susceptibility and onset, and the Pgia12 locus (6 Mbp) associated with low arthritis severity. Thus, we have reached the critical sizes of arthritis-associated genomic loci on mouse chr3 and chr19, which are ready for high-throughput sequencing of genomic DNA.

Original languageEnglish
Pages (from-to)336-345
Number of pages10
JournalGenes and Immunity
Volume13
Issue number4
DOIs
Publication statusPublished - Jun 2012

Keywords

  • Rodent
  • arthritis
  • autoimmunity
  • chromosomes
  • cytokines

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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