Genetic control of anti-Sm autoantibody production in NOD congenic mice narrowed to the Idd9.3 region

Junichiro Irie, Yuehong Wu, David A. Sass, William M. Ridgway

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Anti-Smith (anti-Sm) autoantibodies are directed to proteins in the small-nuclear ribonucleoprotein (snRNP) family and are considered specific for systemic lupus erythematosus (SLE) in both humans and mice. We previously established that NOD.c3c4 mice, carrying B6 and B10 congenic segments from chromosomes 3 and 4 on a nonobese diabetic (NOD) background, and NOD. Idd9R28 mice, carrying a B10 segment on c4 alone, developed significant penetrance of anti-Sm antibody production. Here we determine autoantibody incidence in additional NOD.Idd9 congenic strains and use a congenic mapping approach to narrow the interval necessary for enhanced autoantibody production to a ∼5.6-Mb region containing insulin-dependent diabetes (Idd)9.3. The Idd93 interval contains the candidate molecule cluster of differentiation (CD)137, which is a member of the tumor necrosis factor (TNF) receptor superfamily, functions as an inducible costimulator of T cells, and controls T-B interactions. The NOD and B10 CD137 alleles have sequence polymorphisms and different functional effects on T cells; the NOD CD137 allele mediates weaker T cell proliferative responses and decreased interleukin (IL)-2 production after CD137-mediated costimulation. Our work establishes CD137 as a candidate gene for control of autoantibody production in NOD.Idd9.3 congenic mice.

Original languageEnglish
Pages (from-to)9-14
Number of pages6
JournalImmunogenetics
Volume58
Issue number1
DOIs
Publication statusPublished - 2006 Feb
Externally publishedYes

Fingerprint

Congenic Mice
Inbred NOD Mouse
Autoantibodies
T-Lymphocytes
Inducible T-Cell Co-Stimulator Protein
Alleles
Small Nuclear Ribonucleoproteins
Chromosomes, Human, Pair 4
Chromosomes, Human, Pair 3
Penetrance
Tumor Necrosis Factor Receptors
Nuclear Family
Systemic Lupus Erythematosus
Antibody Formation
Interleukin-2
Anti-Idiotypic Antibodies
Insulin
Incidence
Genes
Proteins

Keywords

  • Anti-Sm antibodies
  • Autoantibodies
  • CD137
  • Congenic mice
  • Nonobese diabetic mouse
  • SLE

ASJC Scopus subject areas

  • Immunology
  • Genetics

Cite this

Genetic control of anti-Sm autoantibody production in NOD congenic mice narrowed to the Idd9.3 region. / Irie, Junichiro; Wu, Yuehong; Sass, David A.; Ridgway, William M.

In: Immunogenetics, Vol. 58, No. 1, 02.2006, p. 9-14.

Research output: Contribution to journalArticle

Irie, Junichiro ; Wu, Yuehong ; Sass, David A. ; Ridgway, William M. / Genetic control of anti-Sm autoantibody production in NOD congenic mice narrowed to the Idd9.3 region. In: Immunogenetics. 2006 ; Vol. 58, No. 1. pp. 9-14.
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