Functional Dissection of Systemic Lupus Erythematosus Using Congenic Mouse Strains

Laurence Morel, Chandra Mohan, Ying Yu, Byron P. Croker, Nana Tian, Alicia Deng, Edward K. Wakeland

Research output: Contribution to journalArticle

223 Scopus citations

Abstract

We describe the in vivo phenotypes associated with three genomic intervals containing systemic lupus erythematosus (SLE)-susceptibility genes derived from the SLE-prone NZM2410 strain on a C57BL/6 genome. These intervals were identified previously via a genome-wide analysis of SLE susceptibility in a (NZM2410 x C57BL/6)F1 x NZM2410 backcross, and transferred independently on a C57BL/6 background to produce three congenic strains: B6.NZMc1 carrying Sle1, B6.NZMc4 carrying Sle2, and B6.NZMc7 carrying Sle3. B6.NZMc1 develops high titers of IgG anti-nuclear autoantibodies in the absence of any severe nephritis. B6.NZMc4 spontaneously develops elevated levels of IgM, but not IgG Abs against several Ags, indicative of polyclonal activation or polyreactivity affecting the B cell lineage. B6.NZMc7 causes the production of IgM and IgG Abs against both nuclear and non-nuclear Ags and the development of severe lupus nephritis. Therefore, our results show that three defined genomic intervals from the NZM2410 SLE-prone strain each contribute specific component phenotypes that have been associated with SLE, which in combination can mediate severe disease.

Original languageEnglish (US)
Pages (from-to)6019-6028
Number of pages10
JournalJournal of Immunology
Volume158
Issue number12
StatePublished - Jun 15 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Morel, L., Mohan, C., Yu, Y., Croker, B. P., Tian, N., Deng, A., & Wakeland, E. K. (1997). Functional Dissection of Systemic Lupus Erythematosus Using Congenic Mouse Strains. Journal of Immunology, 158(12), 6019-6028.