Document Detail


Identification of chromosome intervals from 129 and C57BL/6 mouse strains linked to the development of systemic lupus erythematosus.
MedLine Citation:
PMID:  16943797     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Systemic lupus erythematosus is an autoimmune disease in which complex interactions between genes and environmental factors determine the disease phenotype. We have shown that genes from the non-autoimmune strains 129 and C57BL/6 (B6), commonly used for generating gene-targeted animals, can induce a lupus-like disease. Here, we conducted a genome-wide scan analysis of a cohort of (129 x B6)F2 C1q-deficient mice to identify loci outside the C1qa locus contributing to the autoimmune phenotype described in these mice. The results were then confirmed in a larger dataset obtained by combining the data from the C1q-deficient mice with data from previously reported wild-type mice. Both analyses showed that a 129-derived interval on distal chromosome 1 is strongly linked to autoantibody production. The B6 genome contributed to anti-nuclear autoantibody production with an interval on chromosome 3. Two regions were linked to glomerulonephritis: a 129 interval on proximal chromosome 7 and a B6 interval on chromosome 13. These findings demonstrate that interacting loci between 129 and B6 mice can cause the expression of an autoimmune phenotype in gene-targeted animals in the absence of any disrupted gene. They also indicate that some susceptibility genes can be inherited from the genome of non-autoimmune parental strains.
Authors:
Y Heidari; A E Bygrave; R J Rigby; K L Rose; M J Walport; H T Cook; T J Vyse; M Botto
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-08-31
Journal Detail:
Title:  Genes and immunity     Volume:  7     ISSN:  1466-4879     ISO Abbreviation:  Genes Immun.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-25     Completed Date:  2007-01-12     Revised Date:  2007-08-13    
Medline Journal Info:
Nlm Unique ID:  100953417     Medline TA:  Genes Immun     Country:  England    
Other Details:
Languages:  eng     Pagination:  592-9     Citation Subset:  IM    
Affiliation:
Molecular Genetics and Rheumatology Section, Faculty of Medicine, Imperial College, Hammersmith Campus, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Antinuclear / biosynthesis
Chromosome Mapping
Complement C1q / deficiency,  genetics
Female
Lupus Erythematosus, Systemic / genetics*,  immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Phenotype
Quantitative Trait Loci
Species Specificity
Grant Support
ID/Acronym/Agency:
071467//Wellcome Trust
Chemical
Reg. No./Substance:
0/Antibodies, Antinuclear; 80295-33-6/Complement C1q

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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