Abstract
The dwarf little (lit) mouse is a model for the human hereditary disorder, isolated growth hormone (GH) deficiency type I1. In these animals, dwarfism results from an autosomal recessively inherited gene mutation. The GH gene is present2 but production of GH mRNA is deficient3, resulting in reduced serum GH and concomitantly decreased serum somatomedin4–6. Growth retardation is evident by 15 days of age and adult animals reach approximately one-half normal size1. Mutant mice of both sexes also exhibit a delayed onset of puberty, with males having a high degree of infertility1. As administration of GH restores growth7, we reasoned that growth failure in the mutant mice might be corrected by providing them with sufficient GH by gene therapy. Here we demonstrate that although the rat and human GH genes alone do not restore growth in transgenic mutants, a metallothionein–rat growth hormone fusion gene (MT–rGH) does. Moreover, the fertility of transgenic mutant males is improved; however, female fertility is impaired.
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References
Eicher, E. M. & Beamer, W. G. J. Hered. 67, 87–91 (1976).
Phillips, J. A., Beamer, W. G. & Bartke, A. J. Endocr. 92, 405–407 (1982).
Cheng, T. C., Beamer, W. G., Phillips, J. A., Bartke, A. & Mallonee, R. L. Endocrinology 113, 1669–1678 (1983).
Herington, A. C., Harrison, D. & Graystone, J. Endocr. 112, 2032–2038 (1983).
Nissley, S. P., Knazek, R. A. & Wolff, G. L. Horm. Metab. Res. 12, 158–164 (1980).
McKern, N. M., Cheek, D. B. & Crewther, W. G. Aust. J. biol. Sci. 34, 221–230 (1981).
Beamer, W. G. & Eicher, E. M. J. Endocr. 71, 37–45 (1976).
Barta, A., Richards, R. I., Baxter, J. D. & Shine, J. Proc. natn. Acad. Sc. U.S.A. 78, 4867–4871 (1981).
Seeburg, P. H. DNA 1, 239–249 (1982).
Wagner, E. F., Covarrubias, L., Stewart, T. A. & Mintz, B. Cell 35, 647–655 (1983).
Palmiter, R. D., Norstedt, G., Gelinas, R. E., Hammer, R. E. & Brinster, R. L. Science 222, 809–814 (1983).
Jaenisch, R. et al. Cell 24, 519–529 (1981).
Palmiter, R. D. et al. Nature 300, 611–615 (1982).
Scholnick, S. B., Morgan, B. A. & Hirsh, J. Cell 34, 37–45 (1983).
Spradling, A. C. & Rubin, G. M. Cell 34, 47–57 (1983).
Goldberg, D. A., Posakony, J. W. & Maniatis, T. Cell 34, 59–73 (1983).
Schnieke, A., Harbers, K. & Jaenisch, R. Nature 304, 315–320 (1983).
Palmiter, R. D., Wilkie, T. M., Chen, H. Y. & Brinster, R. L. Cell 36, 869–877 (1984).
Doehmer, J. et al. Proc. natn. Acad. Sci. U.S.A. 79, 2268–2272 (1982).
Brinster, R. L. et al. Cell 27, 223–231 (1981).
Barsh, G. S., Seeburg, P. H. & Gelinas, R. E. Nucleic Acids Res. 11, 3939–3958 (1983).
Brinster, R. L. in Growth, Nutrition and Metabolism of Cells in Culture Vol. 2 (eds Rothblat, G. & Cristofalo, V.) 251–286 (Academic, New York, 1972).
Palmiter, R. D., Chen, H. Y. & Brinster, R. L. Cell 29, 701–710 (1982).
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Hammer, R., Palmiter, R. & Brinster, R. Partial correction of murine hereditary growth disorder by germ-line incorporation of a new gene. Nature 311, 65–67 (1984). https://doi.org/10.1038/311065a0
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DOI: https://doi.org/10.1038/311065a0
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