International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

F54 A Lupus Susceptibility Locus Present in C57BL/10, But Not C57BL/6, Mice

Rebecca Tucker, Stephen Rozzo, Brian Kotzin. Division of Allergy and Clinical Immunology, University of Colorado Health Science Center, Denver. CO 80262

The F1 hybrid of NZB and NZW mice develop an autoimmune disease that is a model of human systemic lupus erythematosis (SLE). These mice spontaneously produce autoantibodies to several nuclear antigens and to the endogenous retroviral glycoprotein gp70, leading to an immune-complex mediated glomerulonephritis. Previous genetic analyses have identified genomic regions from both parental strains contributing to disease susceptibility. In addition, crosses of NZB and C57BL/10 (B10) mice revealed a lupus-susceptibility locus contributed from the non-autoimmune B10 chromosome 13 at 59 cM. This locus was linked with disease in (B10 x NZB)F1 x NZB mice with a c2=6.7 (P=0.01), and linked with autoantibody production to gp70 with a lod score=5.5 (P=4.8 x 10-7). Further backcross studies determined that this locus was not present in C57BL/6 (B6) mice, although B6 and B10 mice are greater than 98% identical. Analysis of SSLPs in the linked region showed only one polymorphic marker (D13Mit290) between B6 and B10 mice.

Initial study of the MGI database demonstrated the presence of several singly- and doubly-linked YAC contigs spanning the linked region. Although D13Mit290 has yet to be placed on these contigs, markers flanking it have been placed on single contigs. An effort is underway to further narrow the genomic region linked with nephritis and autoantibody production in the (B10 x NZB)F1 x NZB backcross mice. In addition, YACs containing SSLPs flanking the polymorphic marker are being screened for the presence of D13Mit290. Any YACs identified in this manner will be analyzed for additional polymorphisms between B6 and B10 genomes to better define the polymorphic region likely to contain the disease-susceptibility gene.

 


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