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 journalArticle

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
Externally publishedYes

Fingerprint

Chromosomes, Human, Pair 19
Chromosomes, Human, Pair 3
Arthritis
Incidence
High-Throughput Nucleotide Sequencing
Proteoglycans
Major Histocompatibility Complex
Genes
Immunization
Rheumatoid Arthritis
Cytokines
T-Lymphocytes

Keywords

  • arthritis
  • autoimmunity
  • chromosomes
  • cytokines
  • Rodent

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Glant, T. T., Adarichev, V. A., Boldizsar, F., Besenyei, T., Laszlo, A., Mikecz, K., & Rauch, T. A. (2012). Disease-promoting and-protective genomic loci on mouse chromosomes 3 and 19 control the incidence and severity of autoimmune arthritis. Genes and Immunity, 13(4), 336-345. https://doi.org/10.1038/gene.2012.2

Disease-promoting and-protective genomic loci on mouse chromosomes 3 and 19 control the incidence and severity of autoimmune arthritis. / Glant, T. T.; Adarichev, V. A.; Boldizsar, F.; Besenyei, T.; Laszlo, A.; Mikecz, K.; Rauch, T. A.

In: Genes and Immunity, Vol. 13, No. 4, 06.2012, p. 336-345.

Research output: Contribution to journalArticle

Glant, TT, Adarichev, VA, Boldizsar, F, Besenyei, T, Laszlo, A, Mikecz, K & Rauch, TA 2012, 'Disease-promoting and-protective genomic loci on mouse chromosomes 3 and 19 control the incidence and severity of autoimmune arthritis', Genes and Immunity, vol. 13, no. 4, pp. 336-345. https://doi.org/10.1038/gene.2012.2
Glant, T. T. ; Adarichev, V. A. ; Boldizsar, F. ; Besenyei, T. ; Laszlo, A. ; Mikecz, K. ; Rauch, T. A. / Disease-promoting and-protective genomic loci on mouse chromosomes 3 and 19 control the incidence and severity of autoimmune arthritis. In: Genes and Immunity. 2012 ; Vol. 13, No. 4. pp. 336-345.
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