Lessons from the NZM2410 model and related strains

L. Morel, E. K. Wakeland

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

SLE susceptibility requires the interplay of an unknown number of genes and equally unidentified triggering events. The past few years have seen significant advances in our understanding of SLE susceptibility through the genetic analysis of murine models. The NZM2410 strain, which is derived from the NZB/WF1 model has played a significant role in these advances. The main advantages presented by this strain over other models are the genetic homozygozity at all loci and an highly penetrant early onset lupus nephritis in both males and females, indicating that the strongest BWF1 susceptibility loci were retained in NZM2410. After identification of NZM2410 susceptibility loci via linkage analyses, congenic strains have been derived in order to convert a polygenic system into a series of monogenic traits. These congenic strains have been analyzed in an integrated process which has provided simultaneously 1) novel functional characterization of the Sle susceptibility loci, 2) high resolution genetic maps that will lead to the identification of the corresponding susceptibility genes by either candidate locus or positional cloning, and 3) insights into the mechanisms by which these loci interact to produce systemic autoimmunity with fatal end-organ damage.

Original languageEnglish (US)
Pages (from-to)423-446
Number of pages24
JournalInternational Reviews of Immunology
Volume19
Issue number4-5
DOIs
StatePublished - Jan 1 2000

Keywords

  • Congenics
  • Genetics
  • Lupus
  • Murine models
  • Polygenic traits

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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