A Novel Locus Regulates Both Retroviral Glycoprotein 70 and Anti-Glycoprotein 70 Antibody Production in New Zealand Mice When Crossed with BALB/c

Lupus-prone New Zealand Black and New Zealand White mice produce high serum levels of the endogenous retroviral envelope protein gp70 and develop an Ab response to this autoantigen as part of their autoimmune disease. Linkage analysis of two crosses involving New Zealand and BALB/c mice mapped these...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2004-04, Vol.172 (8), p.5078-5085
Main Authors: Rigby, Robert J, Rozzo, Stephen J, Gill, Herpreet, Fernandez-Hart, Timothy, Morley, Bernard J, Izui, Shozo, Kotzin, Brian L, Vyse, Timothy J
Format: Article
Language:English
Subjects:
Animals
Antibodies, Viral - biosynthesis
Antibodies, Viral - blood
Chromosome Mapping
Crosses, Genetic
Female
Fv1 gene
Gene Expression Regulation - immunology
Genetic Linkage
Genetic Markers - immunology
Genetic Predisposition to Disease
Glomerulonephritis - genetics
Glomerulonephritis - immunology
Glycoproteins - blood
Glycoproteins - immunology
Mice
Mice, Congenic
Mice, Inbred BALB C
Mice, Inbred NZB
Proteins - genetics
Retroviridae - immunology
Species Specificity
Viral Envelope Proteins - blood
Viral Envelope Proteins - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Lupus-prone New Zealand Black and New Zealand White mice produce high serum levels of the endogenous retroviral envelope protein gp70 and develop an Ab response to this autoantigen as part of their autoimmune disease. Linkage analysis of two crosses involving New Zealand and BALB/c mice mapped these traits to a group of overlapping loci, including a novel locus on proximal chromosome 12. This locus was linked with serum gp70 and the autoimmune response against it. The linkage of serum gp70 levels to a previously described locus on distal chromosome 4 was also confirmed. Sequence analysis of a candidate gene on distal chromosome 4, Fv1, provided support that this gene may be associated with the control of serum gp70 levels in both New Zealand Black and New Zealand White mice. Linkage data and statistical analysis confirmed a close correlation between gp70 Ag and anti-gp70 Ab levels, and together gave support to the concept that a threshold level of gp70 is required for the production of anti-gp70 Abs. Serum levels of anti-gp70 Abs were closely correlated with the presence of renal disease, more so than anti-dsDNA Abs. Understanding the genetic basis of this complex autoantigen-autoantibody system will provide insight into the pathogenesis of lupus in mice, which may have implications for human disease.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.172.8.5078