Abnormal splicing of the leptin receptor in diabetic mice

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

  1. 1

    Hummel, K. P., Dickie, M. M. & Coleman, D. L., Science 153, 1127–1128 (1966).

    ADS  CAS  Article  Google Scholar 

  2. 2

    Coleman D. L. Diabetologia 14, 141–148 (1978).

    CAS  Article  Google Scholar 

  3. 3

    Zhang, Y. et al. Nature 372, 425–432 (1994).

    ADS  CAS  Article  Google Scholar 

  4. 4

    Halaas, J. L. et al. Science 269, 543–546 (1995).

    ADS  CAS  Article  Google Scholar 

  5. 5

    Pelleymounter, M. A. et al. Science 269, 540–543 (1995).

    ADS  CAS  Article  Google Scholar 

  6. 6

    Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R. & Burn, P. Science 269, 546–549 (1995).

    ADS  CAS  Article  Google Scholar 

  7. 7

    Stephens, T. W. et al. Nature 377, 530–534 (1995).

    ADS  CAS  Article  Google Scholar 

  8. 8

    Tartaglia, L. A. et al. Cell 83, 1263–1271 (1995).

    CAS  Article  Google Scholar 

  9. 9

    Bahary, N. et al. Mamm. Genome 4, 511–515 (1993).

    CAS  Article  Google Scholar 

  10. 10

    Modi, W. S., Farrar, W. L. & Om, E. Cytogenet. Cell Genet. 69, 232–234 (1995).

    CAS  Article  Google Scholar 

  11. 11

    Milatovich, A., Bolger, G., Michaeli, T. & Francke, U. Somat. Cell molec. Genet. 20, 75–86 (1994).

    CAS  Article  Google Scholar 

  12. 12

    Church, D. M. et al. Nature Genet. 6, 98–105 (1994).

    CAS  Article  Google Scholar 

  13. 13

    Morgan, J. G., Dolganov, G. M., Robbins, S. E., Hinton, L. M. & Lovett, M. Nucleic Acids Res. 20, 5173–5179 (1992).

    CAS  Article  Google Scholar 

  14. 14

    Kishimoto, T., Taga, T. & Akira, S. Cell 76, 253–262 (1994).

    CAS  Article  Google Scholar 

  15. 15

    Murakami, M. et al. Proc. natn. Acad. Sci. U.S.A. 88, 11349–11353 (1991).

    ADS  CAS  Article  Google Scholar 

  16. 16

    Fukunaga, R., Ishizaka-lkeda, E., Pan, C.-X., Seto, Y. & Nagata, S. EMBO J. 10, 2855–2865 (1991).

    CAS  Article  Google Scholar 

  17. 17

    Lodish, H. et al. Molecular Cell Biology (Scientific American, New York, 1986).

    Google Scholar 

  18. 18

    Maffei, M. et al. Proc. natn. Acad. Sci. U.S.A. 92, 6957–6960 (1995).

    ADS  CAS  Article  Google Scholar 

  19. 19

    Tarton, M. D. et al. Nature 379, 69–72 (1996).

    ADS  Article  Google Scholar 

  20. 20

    Bahary, N., Leibel, R. L., Joseph, L. & Friedman, J. M. Proc. natn. Acad. Sci. U.S.A. 87, 8642–8646 (1990).

    ADS  CAS  Article  Google Scholar 

  21. 21

    Green, E. D. & Olson, M. V. Proc. natn. Acad. Sci. U.S.A. 87, 1213–1217 (1990).

    ADS  CAS  Article  Google Scholar 

  22. 22

    Kusumi, K., Smith, J. S., Segre, J. A., Koos, D. S. & Lander, E. S. Mamm. Genome 4, 391–392 (1993).

    CAS  Article  Google Scholar 

  23. 23

    Riley, J. et al. Nucleic Acids Res. 18, 2887–2890 (1990).

    CAS  Article  Google Scholar 

  24. 24

    Hermanson, G. G., Hoekstra, M. F., McElligott, D. L. & Evans, G. A. Nucleic Acids Res. 19, 4943–4948 (1991).

    CAS  Article  Google Scholar 

  25. 25

    Sternberg, N. Trends Genet. 8, 11–16 (1992).

    CAS  Article  Google Scholar 

  26. 26

    Hartl, D. L. & Nurminsky, D. I. Bio Techniques 15, 201–208 (1993).

    Google Scholar 

  27. 27

    Shizuya, H. Proc. natn. Acad. Sci. U.S.A. 89, 8794–8797 (1992).

    ADS  CAS  Article  Google Scholar 

Download references

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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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