Experimental allergic orchitis in mice. VI. Recombinations within the H-2S/H-2D interval define the map position of the H-2-associated locus controlling disease susceptibility |
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Authors: | Cory Teuscher David L Gasser Scott R Woodward William F Hickey |
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Institution: | (1) Division of Reproductive Biology, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA;(2) Department of Human Genetics, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA;(3) Department of Microbiology, Brigham Young University, Provo, Utah, USA;(4) Department of Pathology, Washington University School of Medicine, St. Louis, Missouri, USA;(5) Present address: Department of Microbiology, Brigham Young University, 775 WIDB, 84602 Provo, UT, USA |
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Abstract: | Susceptibility to autoimmune orchitis is associated with an immune response (Ir) gene (now designated Orch-1) which was preliminarily shown to reside at or near the H-2D subregion of the major histocompatibility complex in the mouse (H-2). In this study, the role of H-2 in controlling both disease susceptibility and the phenotypic expression of infertility associated with autoimmune orchitis has been significantly extended. Of nine C57BL/10SnJ and three BALB/cAnN H-2 congenic strains, only those mice possessing the H-2
d, H-2
p
haplotypes exhibited autoimmune orchitis accompanied by infertility. All other congenic strains, including those expressing the H-2 haplotypes v, q, b, s, r, f, and k were of the low responder phenotype. In addition, disease susceptibility was found to be inherited as a dominant trait in H-2 congenic F1 hybrid mice. In order to map the precise location of the Orch-1 locus within H-2, 32 intra-H-2 recombinant congenic strains possessing defined crossovers in various locations throughout the H-2 region were studied. The results of the analysis indicate that Orch-1 maps within the interval between the H-2S and H-2D regions. Our results also indicate that class II genes, i.e., A and E region-encoded genes, have little discernable effect in controlling disease susceptibility and resistance despite the fact that testicular lesions can be adoptively transferred with Ia-restricted CD4+ effector T cells. A comparison of the Orch-1 alleles with the genotypes of two additional markers which map within the H-2S/H-2D interval suggests the following gene order: H-2S--TNP-Ficoll--Orch-1--Tnfa--H-2D.
Address correspondence and offprint requests to: C. Teuscher. |
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