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Polymorphisms of the tumor necrosis factor alpha locus among autoimmune disease susceptible and resistant inbred rat strains

Genes & Immunity volume 2, pages 229–232 (2001)Cite this article

Abstract

Inbred rat strains manifest remarkable differences in susceptibility/severity to autoimmune disease. MHC alleles strongly influence the pathogenesis of autoimmune disease in rats, but the precise mechanism(s) remain inadequately defined. The TNFα gene is located in the class III region of the MHC. Polymorphisms, influencing either the structure or expression of the TNF protein, might contribute to differences in autoimmune disease susceptibility/severity. We therefore sequenced the Tnf locus using genomic DNA from ACI, BB(DR), BN, DA, F344, and LEW rats that vary in susceptibility/severity to autoimmune diseases. We found 42 polymorphisms among these six strains. Although none of these polymorphisms are predicted to change the amino acid sequence of the TNF protein, several reside in potential non-coding regulatory regions and may influence expression levels. These polymorphisms may serve as good candidates for analysis of TNF expression to elucidate the mechanism(s) by which the MHC regulates susceptibility and/or severity of autoimmune diseases.

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Author notes

  1. T Furuya

    Present address: Institute of Rheumatology, Tokyo Women’s Medical University, 10–22 Kawada-cho, Shinjuku-ku, 162–0054, Tokyo, Japan

  2. JL Salstrom

    Present address: UCLA ACCESS, 172 Molecular Biology Institute, Box 951570, Los Angeles, 90095–1570, CA, USA

Authors and Affiliations

  1. Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, 9000 Rockville Pike, Building 10, Room 9N240, Bethesda, 20892, MD, USA

    T Furuya, B Joe, JL Salstrom, A Hashiramoto, RL Wilder & EF Remmers

  2. Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, 20814–4799, MD, USA

    DE Dobbins

Authors
  1. T Furuya
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  2. B Joe
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  4. A Hashiramoto
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  5. DE Dobbins
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  6. RL Wilder
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  7. EF Remmers
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Corresponding author

Correspondence to EF Remmers.

Additional information

The nucleotide sequence data reported in this paper have been submitted to GenBank and have been assigned the accession numbers listed in the legend to Figure 1. They will be released to the public pending publication of the report.

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Furuya, T., Joe, B., Salstrom, J. et al. Polymorphisms of the tumor necrosis factor alpha locus among autoimmune disease susceptible and resistant inbred rat strains . Genes Immun 2, 229–232 (2001). https://doi.org/10.1038/sj.gene.6363761

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  • DOI: https://doi.org/10.1038/sj.gene.6363761

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