A novel cell model to study the function of the adrenoleukodystrophy-related protein

Journal Article · Fri Mar 03 00:00:00 EST 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2005.12.152· OSTI ID:20798822

Gueugnon, Fabien ^[1]; Volodina, Natalia ^[1]; Taouil, Jaoued Et ^[1]; Lopez, Tatiana E ^[1]; Gondcaille, Catherine ^[1]; Grand, Anabelle Sequeira-Le ^[2]; Mooijer, Petra A.W. ^[3]; Kemp, Stephan ^[3]; Wanders, Ronald J.A. ^[3]; Savary, Stephane ^[1]

---

1. Laboratoire de Biologie Moleculaire et Cellulaire, Faculte des Sciences Gabriel, 21000 Dijon (France)
2. Plate-forme Commune de Cytometrie en Flux, Universite de Bourgogne, Faculte de Medecine-IFR100, 21000 Dijon (France)
3. University of Amsterdam, Academic Medical Center, Genetic Metabolic Diseases Laboratory, Departments of Pediatrics, Emma Children's Hospital, and Clinical Chemistry, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands)

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.

• OSTI ID: 20798822
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 341, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2005.12.152; PII: S0006-291X(05)02929-3; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
GENES
HEPATOMAS
MUTATIONS
PROTEINS
RATS
SUBSTRATES