Multiple loci are linked with anti-red blood cell antibody production in NZB mice − comparison with other phenotypes implies complex modes of action

NJ Lee, RJ Rigby, H Gill, JJ Boyle, L Fossati-Jimack, Bernard J Morley, TJ Vyse

Research output: Contribution to journalArticle

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Abstract

The New Zealand Black (NZB) mouse strain is a model of autoimmune haemolytic anaemia (AHA) and systemic lupus erythematosus (SLE), characterized by the production of anti-red blood cell (RBC) antibodies and anti-nuclear antibodies (ANA), respectively. A linkage analysis was carried out in an (NZB x BALB/c) F-2 cross in order to identify loci involved in the production of both anti-RBC IgM and IgG antibodies. These regions of linkage were compared with linkage data to ANA from the same cohort and other linkage analyses involving New Zealand mice. Four previously described NZB loci linked to anti-RBC antibodies were confirmed, and eight novel loci linked to this trait were also mapped: five of which were of NZB origin, and three derived from the non-autoimmune BALB/c background. A comparison between loci linked with anti-RBC antibodies and ANA demonstrated many that co-localize, suggesting the presence of genes that result in the general breaking of tolerance to self-antigen. Furthermore, the observation that some loci were associated only with the anti-RBC response suggests an antigen specific mechanism in addition to a general breaking of tolerance. A locus linked with anti-RBC antibodies and ANA on distal chromosome 7 in this cohort is orthologous to one on the q arm of human chromosome 11, a region linked to AHA and ANA in human SLE.
Original languageEnglish
Pages (from-to)39-46
Number of pages8
JournalClinical And Experimental Immunology
Volume138
DOIs
Publication statusPublished - Oct 2004

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New Zealand
Antibody Formation
Erythrocytes
Anti-Idiotypic Antibodies
Phenotype
Antibodies
Autoimmune Hemolytic Anemia
Systemic Lupus Erythematosus
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 7
Information Storage and Retrieval
Autoantigens
Human Chromosomes
Immunoglobulin M
Immunoglobulin G
Antigens
Genes

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Multiple loci are linked with anti-red blood cell antibody production in NZB mice − comparison with other phenotypes implies complex modes of action. / Lee, NJ; Rigby, RJ; Gill, H; Boyle, JJ; Fossati-Jimack, L; Morley, Bernard J; Vyse, TJ.

In: Clinical And Experimental Immunology, Vol. 138, 10.2004, p. 39-46.

Research output: Contribution to journalArticle

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