Murine lupus genetics: Lessons learned

Chandra Mohan

Research output: Contribution to journalReview articlepeer-review

50 Scopus citations


Recent reverse genetic studies in murine lupus have taught us the following lessons: (1) Lupus is extremely polygenic; (2) A single locus may be associated with many different phenotypes; (3) What appears to be a single locus may turn out to be a cluster of loci; (4) Different loci facilitate different immunologic steps leading to lupus; (5) Epistatic interactions between loci may engender novel autoimmune phenotypes; (6) Whereas some loci may be pathogenic, others may confer disease resistance; (7) Whereas the expression of some loci is sex-dependent, the expression of others clearly is not; (8) Two or more loci may have an impact on the same phenotype; (9) Lupus susceptibility loci appear to co-cluster with other autoimmunity susceptibility loci; (10) Lupus genes are likely to be polymorphic alleles with subtle impacts, rather than outright mutations with extreme functions. In contrast, forward genetic studies have revealed that molecules that impact apoptosis, the clearance of apoptotic cells, B-cell or T-cell function, and end-organ pathology can all potentially contribute to lupus. Collectively, the loci and genes identified by these two different approaches factorize into a few distinct pathways leading to lupus. Delineating the molecular mediators of these distinct checkpoints is the challenge that lies ahead.

Original languageEnglish (US)
Pages (from-to)352-360
Number of pages9
JournalCurrent Opinion in Rheumatology
Issue number5
StatePublished - Oct 16 2001

ASJC Scopus subject areas

  • Rheumatology


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