Abstract
The rapid progress in the development of molecular technology has resulted in the identification of most of the genes of the heme biosynthesis pathway. Important problems in the pathogenesis and treatment of porphyrias now seem likely to be solved by the possibility of creating animal models and by the transfer of normal genes or cDNAs to target cells. Animal models of porphyrias naturally occur for erythropoietic protoporphyria and congenital erythropoietic porphyria, and different murine models have been or are being created for erythropoietic and hepatic porphyrias. The PBGD knock-out mouse will be useful for the understanding of nervous system dysfunction in acute porphyrias. Murine models of erythropoietic porphyrias are being used for bone-marrow transplantation experiments to study the features of erythropoietic and hepatic abnormalities. Gene transfer experiments have been startedin vitro to look at the feasibility of somatic gene therapy in erythropoietic porphyrias. In particular, we have documented sufficient gene transfer rate and metabolic correction in different CEP disease cells to indicate that this porphyria is a good candidate for treatment by gene therapy in hematopoietic stem cells. With the rapid advancement of methods that may allow more precise and/or efficient gene targeting, gene therapy will become a new therapeutic option for porphyrias.
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Bensidhoum, M., Ged, C., Poirier, C., Guénet, J. L., and Verneuil, H. de (1994).Mammalian Genome 5, 728–730.
Bensidhoum, M., Ged, C., Hombrados, I., Moreau-Gaudry, F., Hift, R. S., Meissner, P., Sturrock, E. D., and Verneuil, H. de (1995).Eur. J. Hum. Genet., in press.
Blaese, R. M. (1990).Hum. Gene Ther. 1, 327–362.
Blaese, R. M. (1993).Hum. Gene Ther. 4, 521–527.
Bloomer, J. R., Morton, K. O., Reuter, R. J., and Ruth, G. R. (1982).Am. J. Hum. Genet. 34, 322–330.
Bloomer, J. R., Weimer, M. K., Bossenmaier, I. C., Snover, D. C., Pyne, W. D., and Ascher, N. L. (1989).Gastroenterologv 97, 188–194.
Bloomer, J. R., Straka, J. G., Hill, H., Weimer, M. K., and Ruth, G. R. (1990).Am. J. Vet. Res. 51, 1144–1146.
Bordignon, C. (1993).Hum. Gene Ther. 4, 513–520.
Bordignon, C., Servida, P., Notarangelo, L. D., Nobili, N., Ferrari, G., Rossini, G., Mavilio, E., and Ugazio, A. G. (1994).Blood 84, suppl. 1: 402a (abstr.).
Boulechfar, S., Da Silva, V., Deybach, J.C., Nordmann, Y., Grandchamp, B., and Verneuil, H. de (1992).Hum. Genet. 88, 320–324.
Boulechfar, S., Lamoril, J., Montagutelli, X., Guénet, J. L., Deybach, J. C., Nordmann, Y., Dailey, H., Grandchamp, B., and Verneuil, H. de (1993).Genomics 16, 645–648.
Brenner, D. A., and Bloomer, J. R. (1979).Yale J. Biol. Med. 52, 449–454.
Caplen, N. J., Alton, E., Middleton, P. G., Dorin, J. R., Stevenson, B. J., Gao, X., Durham, S. R., Jeffery, P. K., Hodson, M. E., Coutelle, C., Huang, L., Porteous, D. J., Williamson, R., and Geddes, D. M. (1995).Nature Medicine 1, 39–46.
Cloue, N. T., and Stephens, E. H. (1944).Nature (London)153, 252.
Deybach, J. C., Verneuil, H. de, Phung, N., Nordmann, Y., Puissant, A., Boffety, B. (1981).J. Lab. Clin. Med. 97, 551.
Deybach, J. C., Verneuil, H. de, Boulechfar, S., Grandchamp, B., and Nordmann, Y. (1990).Blood 75, 1763–1765.
Fang, B., Eisensmith, R. C., Li, X. H. C., Finegold, M. J., Shedlovsky, A., Dove, W., and Woo, S. L. C. (1994).Gene Ther. 1, 247–2354.
Flyger, V., and Levin, E. Y. (1977).Am. J. Pathol. 87, 269.
Giddens, W. E. Jr., Labbe, R. F., Swango, L. J., and Padgett, G. A. (1975).Am. J. Pathol. 80, 367.
Glenn, B. L., Glenn, H. G., and Omtvedt, I. T. (1968).Am. J. Vet. Res. 29, 1653.
Goerz, G., Bolsen, K., Bunselmeyer, S., Schürer, N. Y. (1994).Lancet 344, 337.
Grossman, M., Raper, S. E., Kozarsky, K., Stein, E. A., Engelhardt, J. F., Muller, D., Lupien, P. J., and Wilson, J. M. (1994).Nature Genetics 6, 335–341.
Herbert, A., Corbin, D., Williams, A., Thompson, D., Buckels, J., and Elias, E. (1991).Gastroenterology 100, 1753–1757.
Hoogerbrugge, P. M., Beusechem, V. V., Valerio, D., Moseley, A., Harvey, M., Fischer, A., Debree, M., Gaspar, B., Morgan, G., and Levinsky, R. (1994).Blood 84, suppl.: 402a (abstr).
Jorgensen, S. K., and With, T. K. (1963).Ann. N. Y. Acad. Sci. 104, 701.
Kappas, A., Sassa, S., Galbraith, R. A., and Nordmann, Y. (1989). InThe Metabolic Basis of Inherited Disease: The Porphyrias (Scriver, C. R., Beaudet, A. L., Sly, W., and Valle, D., eds), McGraw-Hill, New York.
Kauffman, L., Evans, D. I. K., Stevens, R. F., and Weinkove, C. (1991).Lancet 337, 1510–1511.
Lamoril, J., Boulechfar, S., Verneuil, H. de, Grandchamp, B., Nordmann, Y., and Deybach, J. C. (1991).Biochem. Biophys. Res. Commun. 181, 594–599.
Ledley, F. D. (1993).Hepatology 18, 1263–1273.
Levin, E. Y. (1968).Science 161, 907.
Levin, E. Y., and Flyger, V. (1973).J. Clin. Invest. 52, 96.
Lindberg, R. L. P., Grandchamp, B., Porcher, C., Ledermann, B., Bürki, K., and Meyer, U. A. (1994). InEur. Soc. Hum. Genet. (abstr. No. 334).
Mion, F. B. C., Fure, J. L., Berger, F., McGregor, B., Perrot, H., Paliard, P. (1992).J. Hepatol. 16, 203–207.
Moreau-Gaudry, F., Ged, C., Barbot, C., Mazurier, F., Boiron, J. M., Bensidhoum, M., Reiffers, J., and Verneuil, H. de (1995a).Hum. Gene Ther. 6, 13–20.
Moreau-Gaudry, F., Mazurier, F., Bensidhoum Ged, C., and Verneuil, H. de (1995b).Blood 85, 1449–1453.
Mulligan, R. C. (1993).Science 260, 926–932.
Nakahashi, Y., Miyazaki, H., Kadota, Y., Naitoh, Y., Inoue, K., Yamamoto, M., Hayashi, N., and Taketani, S. (1993).Hum. Genet. 91, 303–306.
Romeo, G., and Levin, E. Y. (1969).Biochemistry 63, 856–863.
Romeo, G., Glenn, B. L., and Levin, E. Y. (1970a).Biochem. Genet. 4, 719–726.
Romeo, G., Kaback, M. M., and Levin, E. Y. (1970b).Biochem. Genet. 4, 659–664.
Ruth, G. R., Schwartz, S., and Stephenson, B. (1977).Science 198, 199.
Samuel, D., Boboc, B., Bernuau, J., Bismuth, H., and Benhamou, J. P. (1988).Gastroenterology 95, 816–819.
Sarkany, R. P. E., Alexander, G. J. M. A., and Cox, T. M. (1994).Lancet 343, 1394–1395.
Sassa, S., Schwartz, S., and Ruth, G. (1981).J. E.xp. Med. 153, 1094.
Schneider-Yin, X., Taketani, S., Schäfer, B., and Minder, E. I. (1994).Lancet 344, 337.
Straka, J. G., Hill, H. D., Krikava, J. M., Kools, A. M., and Bloomer, J. R. (1991)Am. J. Hum. Genet. 48, 72–78.
Tobias, G. (1964).J. Am. Vet. Med. Assoc. 145, 462.
Tsai, S.-F., Bishop, D. F. and Desnick, R. J. (1988).Proc. Natl. Acad. Sci. USA 85, 7049–7053.
Tutois, S., Montagutelli, X., Da Silva, V., Jouault, I. I., Rouyer-Fessard, P., Leroy-Viard, K., Guénet, J. L., Nordmann, Y., Beuzard, Y., and Deybach, J. C. (1991).J. Clin. Invest. 88, 1730–1736.
Valerio, D. (1992).Hum. Gene Ther. 3, 553–558.
Verneuil, H. de, Moreau-Gaudry, F., Ged, C., Bensidhoum, M., Hombrados, I., Tricoire, J., and Rolland, M. (1995).Arch. Ped., in press.
Verstraeten, L., Van Regemorter, N., Pardou, A., Verneuil, H. de, Da Silva, V., Rodesch, F., Vermeylen, D., Donner, C., Noël, J. C., Nordmann, Y., and Hassoun, A. (1993).Eur. J. Clin. Chem. Clin. Biochem. 31, 121–128.
Warner, C. A., Yoo, H. W., Roberts, A. G., and Desnick, R. J. (1992).J. Clin. Invest. 89, 693–700.
Wilson, J. M., Grossman, M., Raper, S. E., Baker, J. R., Newlan, R. S., and Thoene, J. G. (1992).Hum. Gene Ther. 3, 179–222.
Xu, W., Warner, C. A., and Desnick, R. J. (1995)J. Clin. Invest. 95, 905–912.
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de Verneuil, H., Ged, C., Boulechfar, S. et al. Porphyrias: Animal models and prospects for cellular and gene therapy. J Bioenerg Biomembr 27, 239–248 (1995). https://doi.org/10.1007/BF02110039
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DOI: https://doi.org/10.1007/BF02110039