Endocrine

, Volume 19, Issue 3, pp 257–266

Tissue-specific targeting of the insulin receptor gene

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Abstract

The techniques to study the mechanisms that underlie the pathogenesis of disease processes have been revolutionized by the development of methods that allow spatiotemporal control of gene deletion or gene expression in transgenic and knockout animals. The ability to interfere with the function of a single protein in a specific tissue allows unprecedented flexibility for exploring gene function in both health and disease. The present review will summarize some of the different knockouts and transgenics generated recently to study type 2 diabetes and critically evaluate the techniques used to examine the function of the insulin receptor in two nonclassical insulin target tissues—the pancreatic islet and the central nervous system.

Key Words

Cre/lox insulin receptor islet β-cells brain knockout 

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References

  1. 1.
    Kahn, C. R. (1994). Diabetes 43, 1066–1084.PubMedGoogle Scholar
  2. 2.
    Blakesley, V. A., Butler, A. A., Koval, A. P., Okubo, Y., and LeRoith, D. (1999). In: The IGF system. Rosenfeld, R. and Roberts, C. Jr. (eds.). pp. 143–164.Google Scholar
  3. 3.
    De Meyts, P., Urso, B., Christofferson, C., and Shymko, R. M. (1995). Ann. NY Acad. Sci. 7, 388–401.Google Scholar
  4. 4.
    Cheatham, B. and Kahn, C. R. (1995). Endocr. Rev. 16, 117–142.PubMedGoogle Scholar
  5. 5.
    White, M. F. and Yenush, L. (1998). Curr. Top. Microbiol. Immunol. 228, 179–208.PubMedGoogle Scholar
  6. 6.
    Virkamaki, A., Ueki, K., and Kahn, C. R. (1999). J. Clin. Invest. 103, 931–943.PubMedGoogle Scholar
  7. 7.
    Saltiel, A. R. and Kahn, C. R. (2001). Nature 414, 799–806.PubMedGoogle Scholar
  8. 8.
    White, M. F. (2002). Am. J. Physiol. Endocrinol. Metab. 283, E413-E422.PubMedGoogle Scholar
  9. 9.
    Orban, P. C., Chui, D., and Marth, J. D. (1992). Proc. Natl. Acad. Sci. USA 89, 6861–6865.PubMedGoogle Scholar
  10. 10.
    Ryding, A. D., Sharp, M. G., and Mullins, J. J. (2001). J. Endocrinol. 171, 1–14.PubMedGoogle Scholar
  11. 11.
    Duvillie, B., Cordonnier, N., Deltour, L., et al. (1997). Proc. Natl. Acad. Sci. USA 94, 5137–5140.PubMedGoogle Scholar
  12. 12.
    DeChiara, T. M., Efstratiadis, A., and Robertson, E. J. (1990). Nature 345, 78–80.PubMedGoogle Scholar
  13. 13.
    Liu, J. P., Baker, J., Perkins, J. A., Robertson, E. J., and Efstratiadis, A. (1993). Cell 75, 59–72.PubMedGoogle Scholar
  14. 14.
    Powell-Braxton, L., Hollingshead, P., Warburton, C., et al. (1993). Genes & Development 7, 2609–2617.Google Scholar
  15. 15.
    Woods, K. A., Camacho-Hubner, C., Savage, M. O., and Clark, A. J. L. (1996). N. Engl. J. Med. 335, 1363–1367.PubMedGoogle Scholar
  16. 16.
    Accili, D., Drago, J., Lee, E. J., et al. (1996). Nat. Genet. 12, 106–109.PubMedGoogle Scholar
  17. 17.
    Joshi, R. L., Lamothe, B., Cordonnier, N., et al. (1996). EMBO J. 15, 1542–1547.PubMedGoogle Scholar
  18. 18.
    Elders, M. J., Schedewie, H. K., Olefsky, J., et al. (1982). J. Natl. Med. Assoc. 74, 1195–1210.PubMedGoogle Scholar
  19. 19.
    Taylor, S. I. (1992). Diabetes 41, 1473–1490.PubMedGoogle Scholar
  20. 20.
    Araki, E., Lipes, M. A., Patti, M. E., et al. (1994). Nature 372, 186–190.PubMedGoogle Scholar
  21. 21.
    Tamemoto, H., Kadowaki, T., Tobe, K., et al. (1994). Nature 372, 182–186.PubMedGoogle Scholar
  22. 22.
    Kulkarni, R. N., Winnay, J. N., Daniels, M., et al. (1999). J. Clin. Invest. 104, R69-R75.PubMedGoogle Scholar
  23. 23.
    Kubota, N., Tobe, K., Terauchi, Y., et al. (2000). Diabetes 49, 1880–1889.PubMedGoogle Scholar
  24. 24.
    Aspinwall, C. A., Qian, W. J., Roper, M. G., Kulkarni, R. N., Kahn, C. R., and Kennedy, R. T. (2000). J. Biol. Chem. 275, 22331–22338.PubMedGoogle Scholar
  25. 25.
    Withers, D. J., Gutierrez, J. S., Towery, H., et al. (1998). Nature 391, 900–904.PubMedGoogle Scholar
  26. 26.
    Burks, D. J., de Mora, J. F., Schubert, M., et al. (2000). Nature 407, 377–382.PubMedGoogle Scholar
  27. 27.
    Liu, S. C., Wang, Q., Lienhard, G. E., and Keller, S. R. (1999). J. Biol. Chem. 274, 18093–18099.PubMedGoogle Scholar
  28. 28.
    Fantin, V. R., Wang, Q., Lienhard, G. E., and Keller, S. R. (2000). Am. J. Physiol. Endocrinol. Metab. 278, E127-E133.PubMedGoogle Scholar
  29. 29.
    Ueki, K., Yballe, C. M., Brachmann, S. M., et al. (2002). Proc. Natl. Acad. Sci USA 99, 419–424.PubMedGoogle Scholar
  30. 30.
    Terauchi, Y., Tsuji, T., Satoh, S., et al. (1999). Nat. Genet. 21, 230–235.PubMedGoogle Scholar
  31. 31.
    Mauvais-Jarvis, F., Ueki, K., Fruman, D. A., et al. (2002). J. Clin. Invest. 109, 141–149.PubMedGoogle Scholar
  32. 32.
    Cho, H., Mu, J., Kim, J. K., et al. (2001). Science 292, 1728–1731.PubMedGoogle Scholar
  33. 33.
    Pende, M., Kozma, S. C., Jaquet, M., et al. (2000). Nature 408, 994–997.PubMedGoogle Scholar
  34. 34.
    Mauvais-Jarvis, F., Kulkarni, R. N., and Kahn, C. R. (2002). Clin. Endocrinol. (Oxf.) 57, 1–9.Google Scholar
  35. 35.
    Rhodes, C. J. and White, M. F. (2002). Eur. J. Clin. Invest. 32(Suppl. 3), 3–13.PubMedGoogle Scholar
  36. 36.
    Gu, H., Marth, J. D., Orban, P. C., Mossmann, H., and Rajewsky, K. (1994). Science 265, 103–106.PubMedGoogle Scholar
  37. 37.
    Kulkarni, R. N., Michael, M. D., and Kahn, C. R. (2000). In: Genetic manipulation of receptor expression and function. Accili, D. (ed.). Wiley-Liss: New York, pp. 129–154.Google Scholar
  38. 38.
    Chang, P. Y., Benecke, H., Le Marchand-Brustel, Y., Lawitts, J. A., and Moller, D. E. (1994). J. Biol. Chem. 269, 16034–16040.PubMedGoogle Scholar
  39. 39.
    Chang, P. Y., Goodyear, L. J., Benecke, H., Markuns, J. S., and Moller, D. E. (1995). J. Biol. Chem. 270, 12593–12600.PubMedGoogle Scholar
  40. 40.
    Lauro, D., Kido, Y., Castle, A. L., et al. (1998). Nat. Genet. 20, 294–298.PubMedGoogle Scholar
  41. 41.
    Bruning, J. C., Michael, M. D., Winnay, J. N., et al. (1998). Mol. Cell 2, 559–569.PubMedGoogle Scholar
  42. 42.
    Kim, J. K., Michael, M. D., Previs, S. F., et al. (2000). J. Clin. Invest. 105, 1791–1797.PubMedGoogle Scholar
  43. 43.
    Zisman, A., Peroni, O. D., Abel, D., et al. (2000). Nat. Med. 6, 924–928.PubMedGoogle Scholar
  44. 44.
    Michael, M. D., Kulkarni, R. N., Postic, C., et al. (2000). Mol. Cell 6, 87–97.PubMedGoogle Scholar
  45. 45.
    Bluher, M., Michael, M. D., Peroni, O. D., et al. (2002). Dev. Cell 3, 25–38.PubMedGoogle Scholar
  46. 46.
    Abel, E. D., Peroni, O., Kim, J. K., et al. (2001). Nature 409, 729–733.PubMedGoogle Scholar
  47. 47.
    Kulkarni, R. N. (2002). Biochem. Soc. Trans. 30, 317–322.PubMedGoogle Scholar
  48. 48.
    Van Schravendijk, C. F., Foriers, A., Van den Brande, J. L., and Pipeleers, D. G. (1987). Endocrinol. 121, 1784–1788.Google Scholar
  49. 49.
    Van Schravendijk, C. F., Foriers, A., Hooghe-Peters, E. L., et al. (1985). Endocrinol. 117, 841–848.Google Scholar
  50. 50.
    Harbeck, M. C., Louie, D. C., Howland, J., Wolf, B. A., and Rothenberg, P. L. (1996). Diabetes 45, 711–717.PubMedGoogle Scholar
  51. 51.
    Hirayama, I., Tamemoto, H., Yokota, H., et al. (1999). Diabetes 48, 1237–1244.PubMedGoogle Scholar
  52. 52.
    Kitamura, T., Kido, Y., Nef, S., Merenmies, J., Parada, L. F., and Accili, D. (2001). Mol. Cell Biol. 21, 5624–5630.PubMedGoogle Scholar
  53. 53.
    Porte, D., Jr. (1991). Banting lecture (1990). Diabetes 40, 166–180.PubMedGoogle Scholar
  54. 54.
    Kulkarni, R. N., Bruning, J. C., Winnay, J. N., Postic, C., Magnuson, M. A., and Kahn, C. R. (1999). Cell 96, 329–339.PubMedGoogle Scholar
  55. 55.
    Asfari, M., Janjic, D., Meda, P., Li, G., Halban, P. A., and Wollheim, C. B. (1992). Endocrinol. 130, 167–178.Google Scholar
  56. 56.
    Newgard, C. B. (2002). Lilly Lecture (2001). Diabetes 51, 3141–3150.PubMedGoogle Scholar
  57. 57.
    Kisanuki, K., Kishikawa, H., Araki, E., et al. (1995). Diabetologia 38, 422–429.PubMedGoogle Scholar
  58. 58.
    Pictet, R. and Rutter, W. J. (1972). In: Handbook of physiology. Steiner, D. F. and Freinkel, M. (eds.). American Physiological Society: Washington, DC, pp. 25–66.Google Scholar
  59. 59.
    Gannon, M., Shiota, C., Postic, C., Wright, C. V. E., and Magnuson, M. (2000). Genesis 26, 139–141.PubMedGoogle Scholar
  60. 60.
    Kulkarni, R. N. and Kahn, C. R. (2001). In: Molecular basis of pancreas development and function. Habener, J. F. and Hussain, M. (eds.). Kluwer Academic Publishers: New York, pp. 299–323.Google Scholar
  61. 61.
    Mauvais-Jarvis, F., Virkamaki, A., Michael, M. D., et al. (2000). Diabetes 49, 2126–2134.PubMedGoogle Scholar
  62. 62.
    Kaku, K., Fiedorek, F. T. J., Province, M., and Permutt, M. A. (1988). Diabetes 37, 707–713.PubMedGoogle Scholar
  63. 63.
    Paigen, B. (1995). Am. J. Clin. Nutr. 62, 458S-462S.PubMedGoogle Scholar
  64. 64.
    Gannon, M., Gamer, L. W. and Wright, C. V. (2001). Genes & Development 98, 7475–7480.Google Scholar
  65. 65.
    Bruning, J. C., Gautam, D., Burks, D. J., et al. (2000). Science 289, 2122–2125.PubMedGoogle Scholar
  66. 66.
    Kulkarni, R. N., Holzenberger, M., Shih, D. Q., et al. (2002). Nat. Genet. 31, 111–115.PubMedGoogle Scholar
  67. 67.
    Xuan, S., Kitamura, T., Nakae, J., et al. (2002). J. Clin. Invest. 110, 1011–1019.PubMedGoogle Scholar
  68. 68.
    Withers, D. J., Burks, D. J., Towery, H. H., Altamuro, S. L., Flint, C. L., and White, M. F. (1999). Nat. Genet. 23, 32–40.PubMedGoogle Scholar
  69. 69.
    Garcia-Ocana, A., Takane, K. K., Syed, M. A., Philbrick, W. M., Vasavada, R. C., and Stewart, A. F. (2000). J. Biol. Chem. 275, 1226–1232.PubMedGoogle Scholar
  70. 70.
    Vasavada, R. C., Garcia-Ocana, A., Zawalich, W. S., et al. (2000). J. Biol. Chem. 275, 15399–15406.PubMedGoogle Scholar
  71. 71.
    Vasavada, R. C., Cavaliere, C., D’Ercole, A. J., et al. (1996). J. Biol. Chem. 271, 1200–1208.PubMedGoogle Scholar
  72. 72.
    Laybutt, D. R., Weir, G. C., Kaneto, H., et al. (2002). Diabetes 51, 1793–1804.PubMedGoogle Scholar
  73. 73.
    Silva, J. P., Kohler, M., Graff, C., et al. (2000). Nat. Genet. 26, 336–340.PubMedGoogle Scholar
  74. 74.
    Postic, C., Shiota, M., Niswender, K. D., et al. (1998). J. Biol. Chem. 274, 305–315.Google Scholar
  75. 75.
    Sund, N. J., Vatamaniuk, M. Z., Casey, M., et al. (2001). Genes Dev. 15, 1706–1715.PubMedGoogle Scholar
  76. 76.
    Ahlgren, U., Jonsson, J., Jonsson, L., Simu, K., and Edlund, H. (1998). Genes Dev. 12, 1763–1768.PubMedGoogle Scholar
  77. 77.
    Havrankova, J., Roth, J., and Brownstein, M. (1978). Nature 272, 827–829.PubMedGoogle Scholar
  78. 78.
    Werther, G. A., Hogg, A., Oldfield, B. J., et al. (1987). Endocrinol. 121, 1562–1570.Google Scholar
  79. 79.
    Marks, J. L., Portee, D., Jr., Stahl, W. L., and Baskin, D. G. (1990). Endocrinol. 127, 3234–3236.Google Scholar
  80. 80.
    Baskin, D. G., Figlewicz Lattemann, D., Seely, R. J., Woods, S. C., Porte, D., Jr., and Schwartz, M. W. (1999). Brain Res. 848, 114–123.PubMedGoogle Scholar
  81. 81.
    Schwartz, M. W., Sipols, A. J., Marks, J. L., et al. (1992). Endocrinol. 130, 3608–3616.Google Scholar
  82. 82.
    Heidenreich, K. A. (1993). Ann. NY Acad. Sci. 27, 72–88.Google Scholar
  83. 83.
    Robinson, L. J., Leitner, W., Draznin, B., and Heidenreich, K. A. (1994). Endocrinol. 135, 2568–2573.Google Scholar
  84. 84.
    Jonas, E. A., Knox, R. J., Smith, T. C., Wayne, N. L., Connor, J. A., and Kaczmarek, L. K. (1997). Nature 385, 343–346.PubMedGoogle Scholar
  85. 85.
    Wan, Q., Xiong, Z. G., Man, H. Y., et al. (1997). Nature 388, 686–690.PubMedGoogle Scholar
  86. 86.
    Obici, S., Feng, Z., Karkanias, G., Baskin, D. G., and Rossetti, L. (2002). Nat. Neurosci. 5, 566–572.PubMedGoogle Scholar
  87. 87.
    Takahashi, M., Yamada, T., Tooyama, I., et al. (1996). Neurosci. Lett. 204, 201–204.PubMedGoogle Scholar
  88. 88.
    Frolich, L., Blum-Degen, D., Bernstein, H. G., et al. (1998). J. Neural. Transm. 105, 423–438.PubMedGoogle Scholar
  89. 89.
    Hoyer, S. (1998). J. Neural. Transm. 105, 415–422.PubMedGoogle Scholar
  90. 90.
    Hoyer, S. (2002). J. Neural. Transm. 109, 341–360.PubMedGoogle Scholar
  91. 91.
    Frolich, L., Blum-Degen, D., Riederer, P., and Hoyer, S. (1999). Ann. NY Acad. Sci. 893, 290–293.PubMedGoogle Scholar
  92. 92.
    Alemzadeh, R. and Holshouser, S. (1999). Endocrinol. 140, 3197–3202.Google Scholar
  93. 93.
    Barber, A. J., Nakamura, M., Wolpert, E. B., et al. (2001). J. Biol. Chem. 276, 32814–32821.PubMedGoogle Scholar
  94. 94.
    Lendahl, U., Zimmerman, L. B., and McKay, R. D. (1990). Cell 60, 585–595.PubMedGoogle Scholar
  95. 95.
    Tronche, F., Kellendonk, C., Kretz, O., et al. (1999). Nat. Genet. 23, 99–103.PubMedGoogle Scholar
  96. 96.
    Zulewski, H., Abraham, E. J., Gerlach, M. J., et al. (2001). Diabetes 50, 521–533.PubMedGoogle Scholar
  97. 97.
    Selander, L. and Edlund, H. (2002). Mech. Dev. 113, 189–192.PubMedGoogle Scholar
  98. 98.
    Leiter, E. H. (1989). FASEB J. 3, 2231–2241.PubMedGoogle Scholar
  99. 99.
    Leiter, E. H., Premdas, F., Harrison, D. E., and Lipson, L. G. (1988). FASEB J. 2, 2807–2811.PubMedGoogle Scholar
  100. 100.
    Bueler, H., Fischer, M., Lang, Y., et al. (1992). Nature 356, 577–582.PubMedGoogle Scholar
  101. 101.
    Gerlai, R. (1996). Trends Neurosci. 19, 177–181.PubMedGoogle Scholar
  102. 102.
    Nadeau, J. H. (2001). Nat. Rev. Genet. 2, 165–174.PubMedGoogle Scholar
  103. 103.
    Sanford, L. P., Kallapur, S., Ormsby, I., and Doetschman, T. (2001). In: Gene knockout protocols. Tymms, M. J. and Kola, I. (eds.). Humana Press, Inc.: Totowa, NJ, pp. 217–226.Google Scholar
  104. 104.
    Crawley, J. N., Belknap, J. K., Collins, A., et al. (1996). Psychopharmacology 132, 107–124.Google Scholar
  105. 105.
    Almind, K., Doria, A., and Kahn, C. R. (2001). Nat. Med. 7, 277–279.PubMedGoogle Scholar
  106. 106.
    Wolfer, D. P., Crusio, W. E., and Lipp, H. P. (2002). Trends Neurosci. 25, 336–340.PubMedGoogle Scholar
  107. 107.
    Mutant mice and neuroscience: recommendations concerning genetic background. (1997). Banbury Conference on genetic background in mice. Neuron 19, 755–759.Google Scholar
  108. 108.
    Kulkarni, R. N., Almind, K., Quinn, R. L., Eisenman, D., Kahn, C. R. (2001). ADA (Abstr.).Google Scholar
  109. 109.
    Zhu, Z., Ma, B., Homer, R. J., Zheng, T., and Elias, J. A. (2001). J. Biol. Chem. 276, 25222–25229.PubMedGoogle Scholar
  110. 110.
    Kahn, C. R., Bruning, J. C., Michael, M. D., and Kulkarni, R. N. (2000). J. Pediatr. Endocrinol. Metab. 13(Suppl. 6), 1377–1384.PubMedGoogle Scholar
  111. 111.
    Katz, E. B., Stenbit, A. E., Hatton, K., DePinho, R., and Charron, M. J. (1995). Nature 377, 151–155.PubMedGoogle Scholar
  112. 112.
    Chen, W. S., Xu, P. Z., Gottlob, K., et al. (2001). Genes Dev. 15, 2203–2208.PubMedGoogle Scholar
  113. 113.
    Maeda, N., Shimomura, I., Kishida, K., et al. (2002). Nat. Med. 8, 731–737.PubMedGoogle Scholar
  114. 114.
    Kubota, N., Terauchi, Y., Yamauchi, T., et al. (2002). J. Biol. Chem. 277, 25863–25866.PubMedGoogle Scholar
  115. 115.
    Ma, K., Cabrero, A., Saha, P. K., et al. (2002). J. Biol. Chem. 277, 34658–34661.PubMedGoogle Scholar
  116. 116.
    Yakar, S., Liu, J. L., Stannard, B., Butler, A., Accili, D., Sauer, B., LeRoith, D. (1999). Proc. Natl. Acad. Sci. USA 96, 7324–7329.PubMedGoogle Scholar
  117. 117.
    Liu, J. L., Yakar, S., and LeRoith, D. (2000). Endocrinol. 141, 4436–4441.Google Scholar
  118. 118.
    Yakar, S., Liu, J. L., Fernandez, A. M., et al. (2001). Diabetes 50, 1110–1118.PubMedGoogle Scholar
  119. 119.
    Moller, D. E., Chang, P. Y., Yaspelkis, B. B. III, Flier, J. S., Wallberg-Henriksson, H., and Ivy, J. L. (1996). Endocrinol. 137, 2397–2405.Google Scholar
  120. 120.
    Fernandez, A. M., Kim, J. K., Yakar, S., et al. (2001). Genes Dev. 15, 1926–1934.PubMedGoogle Scholar
  121. 121.
    McCaffrey, A. P., Meuse, L., Pham, T. T., Conklin, D. S., Hannon G. J., and Kay, M. A. (2002). Nature 418(6893), 38–39.PubMedGoogle Scholar
  122. 122.
    Brummelkamp, T. R., Bernards, R., and Agami, R. (2002). Science 296(5567), 550–553.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  1. 1.Research Division, Joslin Diabetes Center, Department of MedicineHarvard Medical SchoolBoston

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