The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein

Abstract

Adrenoleukodystrophy Is a severe genetic demye-llnating disease associated with an Impairment of /S-oxldatlon of very long chain fatty acids (VLCFA) In peroxisomes. Earlier studies had suggested that a deficiency In VLCFA CoA synthetase was the primary defect. A candidate adrenoleukodystrophy gene has recently been cloned and was found unexpectedly to encode a putative ATP-blnding cassette transporter. We have raised monoclonal antibodies against this protein, that detect a 75kDa band. This protein was absent in several patients with adrenoleukodystrophy. Immunofluorescence and Immunoelectron microscopy showed that the adrenoleukodystrophy protein (ALDP) is associated with the peroxisomal membrane. Distinct Immunofluorescence patterns were observed in cell lines from patients with Zellweger syndrome (a peroxi-somal biogenesis disorder) belonging to different complementation groups