title: A novel cell model to study the function of the adrenoleukodystrophy-related protein.
abstract: X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder due to mutations in the ABCD1 (ALD) gene. ALDRP, the closest homolog of ALDP, has been shown to have partial functional redundancy with ALDP and, when overexpressed, can compensate for the loss-of-function of ALDP. In order to characterize the function of ALDRP and to understand the phenomenon of gene redundancy, we have developed a novel system that allows the controlled expression of the ALDRP-EGFP fusion protein (normal or non-functional mutated ALDRP) using the Tet-On system in H4IIEC3 rat hepatoma cells. The generated stable cell lines express negligible levels of endogenous ALDRP and doxycycline dosage-dependent levels of normal or mutated ALDRP. Importantly, the ALDRP-EGFP protein is targeted correctly to peroxisome and is functional. The obtained cell lines will be an indispensable tool in our further studies aimed at the resolution of the function of ALDRP to characterize its potential substrates in a natural context.
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire, Faculté des Sciences Gabriel, Dijon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Gueugnon
authors.forename: Natalia
authors.initials: N
authors.lastname: Volodina
authors.forename: Jaoued Et
authors.initials: JE
authors.lastname: Taouil
authors.forename: Tatiana E
authors.initials: TE
authors.lastname: Lopez
authors.forename: Catherine
authors.initials: C
authors.lastname: Gondcaille
authors.forename: Anabelle Sequeira-Le
authors.initials: AS
authors.lastname: Grand
authors.forename: Petra A W
authors.initials: PA
authors.lastname: Mooijer
authors.forename: Stephan
authors.initials: S
authors.lastname: Kemp
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Stéphane
authors.initials: S
authors.lastname: Savary
mesh_terms: D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000326:Adrenoleukodystrophy / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015202:Protein Engineering / Q000379:methods; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection / Q000379:methods
chemical_list: C431694:ABCD2 protein, human; D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters; D011993:Recombinant Fusion Proteins