International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 42 - IN BXSB MICE, WHICH SPONTANEOUSLY DEVELOP THE COMPLEX TRAIT SLE, EXPRESSION OF THE AUTOANTIGEN, gp70, IS CONTROLLED BY A SINGLE LOCUS ON CHROMOSOME 13

Dr. Bernard J. Morley
Imperial College
Rheumatology Section
Hammersmith Campus
Du Cane Road
London W12 0NN
U.K.

Co-Authors: 1)Haywood MEK, 1)Vyse TJ, 1)McDermott A, 2)Thompson EM, 3)Ida A, 1)Walport MJ, 3)Izui S
Institutions: 1)Rheumatology Section, Imperial College School of Medicine 2)Department of Histopathology, St Mary's Hospital 3)Department of Pathology, C.M.U.,

Retroviral envelope glycoprotein, gp70, is present in the sera of immunologically normal and autoimmune-prone strains of mice.  However, only lupus-prone mice spontaneously develop anti-gp70 antibodies and these have been implicated in the development of nephritis.  We investigated the genetic factors that affect the production of both free serum gp70 and anti-gp70 antibodies in the lupus-prone BXSB mouse strain, by analysing (BXSB x (C57BL/10 x BXSB)F1) and (C57BL/10 x (C57BL/10 x BXSB)F1) backcross male mice.  Production of gp70 mapped to a single major locus located on chromosome 13 (Bxs6) with a maximum LOD of 36.7 (P = 1.6 x 10-38).  The level of anti-gp70 antibodies was highly dependent on Bxs6-directed gp70 production, and high titre autoantibody production only occurred when serum gp70 levels were greater than a threshold value of approximately 4.0mgml-1.  A remarkable association was observed between high levels of anti-gp70 antibodies and severe nephritis in Bxs6 homozygote mice.  A further mapping study has identified a novel BXSB interval on chromosome 9, Gp1, associated specifically with the production of anti-gp70 antibodies.  This work has demonstrated that a single locus is responsible for a specific subset of autoantibody production in a complex trait.


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