Abstract
MUTATIONS in the mouse diabetes(db) gene result in obesity and diabetes in a syndrome resembling morbid human obesity1. Previous data suggest that the db gene encodes the receptor for the obese(ob) gene product, leptin2–7. A leptin receptor was recently cloned from choroid plexus and shown to map to the same 6-cM interval on mouse chromosome 4 as db8. This receptor maps to the same 300-kilobase interval as db, and has at least six alternatively spliced forms. One of these splice variants is expressed at a high level in the hypothalamus, and is abnormally spliced in C57BL/Ks db/db mice. The mutant protein is missing the cytoplasmic region, and is likely to be defective in signal transduction. This suggests that the weight-reducing effects of leptin may be mediated by signal transduction through a leptin receptor in the hypothalamus.
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References
Hummel, K. P., Dickie, M. M. & Coleman, D. L., Science 153, 1127–1128 (1966).
Coleman D. L. Diabetologia 14, 141–148 (1978).
Zhang, Y. et al. Nature 372, 425–432 (1994).
Halaas, J. L. et al. Science 269, 543–546 (1995).
Pelleymounter, M. A. et al. Science 269, 540–543 (1995).
Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R. & Burn, P. Science 269, 546–549 (1995).
Stephens, T. W. et al. Nature 377, 530–534 (1995).
Tartaglia, L. A. et al. Cell 83, 1263–1271 (1995).
Bahary, N. et al. Mamm. Genome 4, 511–515 (1993).
Modi, W. S., Farrar, W. L. & Om, E. Cytogenet. Cell Genet. 69, 232–234 (1995).
Milatovich, A., Bolger, G., Michaeli, T. & Francke, U. Somat. Cell molec. Genet. 20, 75–86 (1994).
Church, D. M. et al. Nature Genet. 6, 98–105 (1994).
Morgan, J. G., Dolganov, G. M., Robbins, S. E., Hinton, L. M. & Lovett, M. Nucleic Acids Res. 20, 5173–5179 (1992).
Kishimoto, T., Taga, T. & Akira, S. Cell 76, 253–262 (1994).
Murakami, M. et al. Proc. natn. Acad. Sci. U.S.A. 88, 11349–11353 (1991).
Fukunaga, R., Ishizaka-lkeda, E., Pan, C.-X., Seto, Y. & Nagata, S. EMBO J. 10, 2855–2865 (1991).
Lodish, H. et al. Molecular Cell Biology (Scientific American, New York, 1986).
Maffei, M. et al. Proc. natn. Acad. Sci. U.S.A. 92, 6957–6960 (1995).
Tarton, M. D. et al. Nature 379, 69–72 (1996).
Bahary, N., Leibel, R. L., Joseph, L. & Friedman, J. M. Proc. natn. Acad. Sci. U.S.A. 87, 8642–8646 (1990).
Green, E. D. & Olson, M. V. Proc. natn. Acad. Sci. U.S.A. 87, 1213–1217 (1990).
Kusumi, K., Smith, J. S., Segre, J. A., Koos, D. S. & Lander, E. S. Mamm. Genome 4, 391–392 (1993).
Riley, J. et al. Nucleic Acids Res. 18, 2887–2890 (1990).
Hermanson, G. G., Hoekstra, M. F., McElligott, D. L. & Evans, G. A. Nucleic Acids Res. 19, 4943–4948 (1991).
Sternberg, N. Trends Genet. 8, 11–16 (1992).
Hartl, D. L. & Nurminsky, D. I. Bio Techniques 15, 201–208 (1993).
Shizuya, H. Proc. natn. Acad. Sci. U.S.A. 89, 8794–8797 (1992).
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Lee, GH., Proenca, R., Montez, J. et al. Abnormal splicing of the leptin receptor in diabetic mice. Nature 379, 632–635 (1996). https://doi.org/10.1038/379632a0
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DOI: https://doi.org/10.1038/379632a0
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