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Scientific article
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Dissection of BXSB lupus phenotype using mice congenic for chromosome 1 demonstrates that separate intervals direct different aspects of disease

Published inThe Journal of immunology, vol. 173, no. 7, p. 4277-4285
Publication date2004
Abstract

To dissect the individual effects of the four non-MHC, autosomal loci (Bxs1 to Bxs4) that contribute to SLE susceptibility in BXSB mice, we generated congenic lines from chromosome 1 on a C57BL/10.Y(BXSB) (B10.Yaa) background for the intervals (values in megabases (Mb)) Bxs1 (46.3-89.2 Mb), Bxs1/4 (20.0-65.9 Mb), Bxs1/2 (64.4-159.0 Mb), and Bxs2/3 (105.4-189.0 Mb). Glomerulonephritis, qualitatively similar to that seen in the parental BXSB strain, developed in three of these congenic strains. Early onset, severe disease was observed in B10.Yaa.BXSB-Bxs2/3 congenic mice and caused 50% mortality by 12 mo. In B10.Yaa.BXSB-Bxs1/4 mice disease progressed more slowly, resulting in 13% mortality at 12 mo. The progression of renal disease in both of these strains was correlated with the level of anti-dsDNA Abs. B10.Yaa.BXSB-Bxs1 mice, despite their genetic similarity to B10.Yaa.BXSB-Bxs1/4 mice, developed a low-grade glomerulonephritis in the absence of anti-dsDNA Abs. Thus, Bxs4 directed an increase in titer and spectrum of autoantibodies, whereas Bxs1 promoted the development of nephritis. The Bxs2 interval was linked to the production of anti-dsDNA Abs without concomitant glomerulonephritis. In contrast, the Bxs3 interval was sufficient to generate classic lupus nephritis in a nonautoimmune-prone strain. Immune phenotype differed between controls and congenics with a significant increase in B220(+) cells in BXSB and B10.Yaa.BXSB-Bxs2/3, and an increase in CD4 to CD8 ratio in both BXSB and B10.Yaa.BXSB-Bxs1/4. Disease in the Bxs3 mice was delayed in comparison to the BXSB parental strain, emphasizing the necessity for multiple interactions in the production of the full BXSB phenotype.

Keywords
  • Animals
  • Autoantibodies/biosynthesis
  • *Chromosome Mapping
  • Crosses, Genetic
  • Female
  • Genetic Markers/immunology
  • *Genetic Predisposition to Disease
  • Immunophenotyping
  • Linkage (Genetics)
  • Lupus Erythematosus, Systemic/*genetics/*immunology/mortality
  • Lupus Nephritis/genetics/immunology
  • Male
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • *Phenotype
  • Severity of Illness Index
  • Splenomegaly/genetics/immunology
Affiliation Not a UNIGE publication
Citation (ISO format)
HAYWOOD, M. E. et al. Dissection of BXSB lupus phenotype using mice congenic for chromosome 1 demonstrates that separate intervals direct different aspects of disease. In: The Journal of immunology, 2004, vol. 173, n° 7, p. 4277–4285. doi: 10.4049/jimmunol.173.7.4277
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Article
accessLevelRestricted
Identifiers
ISSN of the journal0022-1767
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