Correction by gene expression of biochemical abnormalities in fibroblasts from Zellweger patients.
Zellweger syndrome is a prototype of peroxisomal biogenesis disorders and a fatal autosomal recessive disease with no effective therapy. We identified nine genetic complementation groups of these disorders, and mutations in peroxisome assembly factor-1 (PAF-1) and the 70-kD peroxisomal membrane protein (PMP70) genes have been detected by our group F and Roscher's group 1, respectively. We now describe permanent recovery from generalized peroxisomal abnormalities in fibroblasts of a Zellweger patient from group F, such as biochemical defects of peroxisomal beta-oxidation, plasmalogen biosynthesis, and morphologic absence of peroxisomes, by stable transfection of human cDNA encoding PAF-1. In the light of these observations, we designed a gene expression system using fibroblasts from patients with peroxisomal biogenesis disorders. In Zellweger fibroblasts obtained from Roscher's group 1 and transfected with human cDNA encoding PMP70, peroxisomes were not morphologically identifiable, and peroxisomal function did not normalize.
Shimozawa
N
N
Department of Pediatrics, Gifu University School of Medicine, Japan.
Suzuki
Y
Y
Tomatsu
S
S
Tsukamoto
T
T
Osumi
T
T
Fujiki
Y
Y
Kamijo
K
K
Hashimoto
T
T
Kondo
N
N
Orii
T
T
D018528:ATP-Binding Cassette Transporters; D000217:Acyltransferases / Q000378:metabolism; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D005816:Genetic Complementation Test; D015316:Genetic Therapy; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D008830:Microbodies / Q000378:metabolism; D010084:Oxidation-Reduction; D000074428:Peroxisomal Biogenesis Factor 2; D014162:Transfection; D015211:Zellweger Syndrome / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy
C063305:ABCD3 protein, human; D018528:ATP-Binding Cassette Transporters; D018076:DNA, Complementary; D005227:Fatty Acids; D008565:Membrane Proteins; D000074428:Peroxisomal Biogenesis Factor 2; D000217:Acyltransferases; C020051:glycerone-phosphate O-acyltransferase; C010210:lignoceric acid