Mammalian Genome

, Volume 4, Issue 1, pp 37–42 | Cite as

Genetic mapping of the athymic nude (RNU) locus in the rat to a region on Chromosome 10

  • Joseph M. Cash
  • Elaine F. Remmers
  • Ellen A. Goldmuntz
  • Leslie J. Crofford
  • Hongbin Zha
  • Carl T. Hansen
  • Ronald L. Wilder
Original Contributions
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Accepted:

Abstract

The nude trait in the rat is transmitted in an autosomal recessive manner and is associated with thymic aplasia, T-cell deficiency, and hairlessness. Congenic rats homozygous for the RNU (Rowett nude) locus are important models in the study of inflammatory disease, tumor growth, and transplant rejection. The RNU locus has not been previously mapped, and the nature of the gene product is unknown. To determine the map location of this gene, a single F344.rnu/rnu (athymic nude congenic Fischer rat) male congenic rat was bred with 3 LEW/N (NIH stock Lewis rat) female rats to produce F1 progeny. Twelve F1 brother-sister breeding pairs were established. Forty-nine phenotypically nude F2 offspring (198 total) were obtained. Linkage analysis done on F2 DNA revealed highly significant cosegregation between the nude phenotype and eight polymorphic markers located on Chromosome (Chr) 10. The tightest linkages were with: MYH3 (embryonic, skeletal myosin heavy chain) and SHBG (sex hormone-binding globulin), giving 2 point lod scores of 20.2, and 20.0, respectively. The map order and map distances, determined by multipoint linkage calculations, were: RR24-(16.1 cM)-MYH3-(3.5 cM)-SHBG-(4.7 cM)-RNU-(11.9 cM)-F16F2-(24.1 cM)-CLATP (citrate lyase ATPase)-(2.4 cM)-ACE (angiotensin converting enzyme)/PPY (pancreatic polypeptide)-(14.1 cM)-RR1023. The position of the RNU locus in the rat corresponds closely with that of the recently reported nu locus in the mouse. This finding suggests that the nude phenotype in the rat and the mouse arise from defects in homologous genes.

Keywords

Angiotensin Converting Enzyme Myosin Heavy Chain Pancreatic Polypeptide Skeletal Myosin Autosomal Recessive Manner 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. Berridge, M.V., O'Kech, N., McNeilage, L.J., Heslop, B.F., and Moore, R.: Rat mutant (nznu) showing “nude” characteristics. Transplantation 27: 410–413, 1979.Google Scholar
  2. Case, J.P., Sano, H., Lafyatis, R., Remmers, E.F., Kumkumian, G.K., and Wilder, R.L.: Transin/stromelysin expression in the synovium of rats with experimental erosive arthritis. J Clin Invest 84: 1731–1740, 1989.Google Scholar
  3. Davisson, M.T., Lalley, P.A., Peters, J., Doolittle, J.P., Hillyard, A.L., and Searle, A.G.: Report of the comparative committee for human, mouse, and other rodents. Cytogenet Cell Genet 58: 1152–1189, 1991.Google Scholar
  4. D'Inca, R., Ernst, P., Hunt, R.H., and Perdue, M.H.: Role of T lymphocytes in intestinal mucosal injury. Inflammatory changes in athymic nude rats. Dig Dis Sci 37: 33–39, 1992.Google Scholar
  5. Festing, M.F.W., May, D., Connors, T.A., Lovell, D., and Sparrow, S.: An athymic mutation in the rat. Nature 274: 365–366, 1978.Google Scholar
  6. Hall, J.M., Lee, M.K., Newman, B., Morrow, J.E., Anderson, L.A., Huey, B., and King, M.C.: Linkage of early-onset breast cancer to chromosome 17q21. Science 250: 1684–1689, 1990.Google Scholar
  7. Hedrich, H.J.: Catalogue of mutant genes and polymorphic loci. In H.J. Hedrich (ed.), Genetic Monitoring of Inbred Strains of Rats, pp. 289–489, Gustav Fischer Verlag, Stuttgart, 1990.Google Scholar
  8. Hilbert, P., Lindpaintner, K., Beckmann, J.S., Serikawa, T., Soubrier, F., Dubay, C., Cartwright, P., De Gouyon, B., Julier, C., Takahasi, S., Vincent, M., Ganten, D., Goerges, M., and Lathrop, G.M.: Chromosomal mapping of two genetic loci associated with blood-pressure regulation in hereditary hypertensive rats. Nature 353: 521–529, 1991.Google Scholar
  9. Hillyard, A.L., Doolittle, D.P., Davisson, M.T., and Roderick, T.H.: Locus map of mouse with comparative map points of human on mouse. The Jackson Laboratory. Bar Harbor, Maine, March 1992.Google Scholar
  10. Jacob, H.J., Lindpainter, K., Lincoln, S.E., Kusumi, K., Bunker, R.K., Mao, Y.P., Ganten, D., Dzau, V.J., and Lander, E.S.: Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell 67: 213–224, 1991.Google Scholar
  11. Lake, S.P., Chamberlain, J., Bassett, P.D., London, N.J.M., Walczak, K., Bell, P.R.F., and James, R.F.L.: Successful reversal of diabetes in nude rats by transplantation of isolated adult human islets of Langerhans. Diabetes 38: 244–248, 1989.Google Scholar
  12. Lander, E.S., Green, P., Abrahamson, J., Barlow, A., Daly, M., Lincoln, S., and Newburg, L.: MAPMAKER: an interactive computer package for constructing genetic linkage maps of experimental and natural populations. Genomics 1: 174–181, 1987.Google Scholar
  13. Maniatis, T., Fritsch, E.F., and Sambrook, J.: Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., p. 280, 1982.Google Scholar
  14. Olden, K.: Human tumor metastasis model in athymic nude rats. J Natl Cancer Inst 80: 340–341, 1990.Google Scholar
  15. Remmers, E.F., Goldmuntz, E., Cash, J.M., Crofford, L.J., Misiewicz-Poltorak, B., Zha, H., and Wilder, R.L.: Genetic map of 9 polymorphic loci comprising a single linkage group on rat chromosome 10: evidence for linkage conservation with human chromosome 17 and mouse chromosome 11. Genomics, in press, 1992.Google Scholar
  16. Sano, H., Forough, R., Maier, J.A.M., Case, J.P., Jackson, A., Engleka, K., Macaig, T., and Wilder, R.L.: Detection of high levels of heparin-binding growth factor-1 (acidic fibroblast growth factor) in inflammatory arthritic joints. J Cell Biol 110: 1417–1421, 1990.Google Scholar
  17. Sano, H., Hla, T., Maier, J.A.M., Crofford, L.J., Case, J.P., Macaig, T., and Wilder, R.L.: In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis and rats with adjuvant and streptococcal cell wall arthritis. J Clin Invest 89: 97–107, 1992.Google Scholar
  18. Schwinzer, R., Hedrich, H.J., and Wonigeit, K.: T cell differentiation in athymic nude rats (rnu/rnu): demonstration of a distorted T cell subset structure by flow cytometric analysis. Eur J Immunol 19: 1841–1847, 1989.Google Scholar
  19. Takahashi, T., Shimizu, A., Sakai, T., Endo, Y., Osowa, N., Shisa, H., and Honjo, T.: Mapping of the nu gene using congenic nude strains and in situ hybridization. J Exp Med 175: 873–876, 1992.Google Scholar
  20. Vos, J.G., Berkvens, J.M., and Kruijt, B.C.: The athymic nude rat. I. Morphology of lymphoid and endocrine organs. Clin Immunol Immunopathol 15: 213–228, 1980.Google Scholar
  21. Wallace, M.R., Marchuk, D.A., Andersen, L.B., Lechter, R., Odeh, H.M., Saulino, A.M., Fountain, J.W., Brereton, A., Nicholson, J., Mitchell, A.L., Brownstein, B.H., and Collins, F.C.: Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science 249: 181–186, 1990.Google Scholar
  22. Wilder, R.L., Allen, J.B., and Hansen, C.: Thymus-dependent and-independent regulation of Ia antigen expression in situ by cells in the synovium of rats with streptococcal cell wall-induced arthritis. J Clin Invest 79: 1160–1171, 1987.Google Scholar
  23. Williams, J.G.K., Kubelik, A.R., Livak, K.J., Rafalski, J.A., and Tingley, S.V.: DNA polymorphisms amplified by arbitrary primers are useful as genetic markers. Nucleic Acids Res 18: 6531–6536, 1990.Google Scholar
  24. Zeifer, A., Jacobs, T., Hedrich, H.J., and Steitz, H.M.: Pneumocystis carinii-infections in immunosuppressed and in thymus deficient rats. Zbl Bakt AA 258: 387 (abstract), 1984.Google Scholar

Copyright information

© Springer-Verlag New York Inc 1993

Authors and Affiliations

  • Joseph M. Cash
    • 1
  • Elaine F. Remmers
    • 1
  • Ellen A. Goldmuntz
    • 1
  • Leslie J. Crofford
    • 1
  • Hongbin Zha
    • 1
  • Carl T. Hansen
    • 2
  • Ronald L. Wilder
    • 1
  1. 1.Arthritis and Rheumatism BranchNational Institute of Arthritis, Musculoskeletal and Skin DiseasesBethesdaUSA
  2. 2.Genetic Resources Section, Veterinary Resources BranchNational Institutes of HealthBethesdaUSA

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