Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Successful therapeutic effect in a mouse model of erythropoietic protoporphyria by partial genetic correction and fluorescence-based selection of hematopoietic cells
Autore:
Fontanellas, A; Mendez, M; Mazurier, F; Cario-Andre, M; Navarro, S; Ged, C; Taine, L; Geronimi, F; Richard, E; Moreau-Gaudry, F; de Salamanca, RE; de Verneuil, H;
Indirizzi:
Univ Madrid, Hosp 12 Octubre, Ctr Invest, Madrid 28041, Spain Univ MadridMadrid Spain 28041 Octubre, Ctr Invest, Madrid 28041, Spain Univ Bordeaux 2, Lab Pathol Mol & Therapie Genique, F-33076 Bordeaux, France Univ Bordeaux 2 Bordeaux France F-33076 enique, F-33076 Bordeaux, France CHU Pellegrin, Genet Lab, Bordeaux, France CHU Pellegrin Bordeaux France HU Pellegrin, Genet Lab, Bordeaux, France
Titolo Testata:
GENE THERAPY
fascicolo: 8, volume: 8, anno: 2001,
pagine: 618 - 626
SICI:
0969-7128(200104)8:8<618:STEIAM>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
FERROCHELATASE GENE; TRANSDUCED CELLS; LIVER-FAILURE; HOUSE MOUSE; EXPRESSION; PORPHYRIA; DISEASE; COMPLICATIONS; INHERITANCE; DEFICIENCY;
Keywords:
animal model porphyria; cutaneous photosensitivity; genetic disease; bone marrow; gene transfer; retrovirus;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Fontanellas, A Univ Madrid, Hosp 12 Octubre, Ctr Invest, Avenida Cordoba,Km 5-400, Madrid28041, Spain Univ Madrid Avenida Cordoba,Km 5-400 Madrid Spain 28041 in
Citazione:
A. Fontanellas et al., "Successful therapeutic effect in a mouse model of erythropoietic protoporphyria by partial genetic correction and fluorescence-based selection of hematopoietic cells", GENE THER, 8(8), 2001, pp. 618-626

Abstract

Erythropoietic protoporphyria is characterized clinically by skin photosensitivity and biochemically by a ferrochelatase deficiency resulting in an excessive accumulation of photoreactive protoporphyrin in erythrocytes, plasma and other organs. The availability of the Fech(m1Pas)/Fech(m1Pas) murinemodel allowed us to test a gene therapy protocol to correct the porphyric phenotype. Gene therapy was performed by ex vivo transfer of human ferrochelatase cDNA with a retroviral vector to deficient hematopoietic cells, followed by re-injection of the transduced cells with or without selection in the porphyric mouse. Genetically corrected cells were separated by FAGS fromdeficient ones by the absence of fluorescence when illuminated under ultraviolet light. Five months after transplantation, the number of fluorescent erythrocytes decreased from 61% (EPP mice) to 19% for EPP mice engrafted with low fluorescent selected BM cells. Absence of skin photosensitivity was observed in mice with less than 20% of fluorescent RBC. A partial phenotypic correction was found for animals with 20 to 40% of fluorescent RBC. In conclusion, a partial correction of bone marrow cells is sufficient to reverse the porphyric phenotype and restore normal hematopoiesis. This selection system represents a rapid and efficient procedure and an excellent alternative to the use of potentially harmful gene markers in retroviral vectors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 08:40:08