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Title: The correction of biochemical abnormalities in fibroblasts of a Zellweger patient by gene expression

Abstract

Zellweger syndrome is a prototype of peroxisome-deficient disorders and a fatal autosomal recessive disease with no effective therapy. We identified nine genetic complementation groups of these disorders among several laboratories, and mutations in peroxisome assembly factor-1 (PAF-1) and the 70-kDa peroxisomal membrane protein (PMP70) genes have been described in Zellweger patients from our group F and Roscher`s group 1, respectively. We now succeed the permanent recovery of generalized peroxisomal abnormalities in fibroblasts of a Zellweger patient from the group F by the stable transfection of human cDNA encoding PAF-1. In the transfectants, a number of peroxisomal dysfunctions such as lignocelic acid oxidation, dihydroxyacetone phosphate acyltransferase activity and biogenesis of peroxisomal {beta}-oxidation enzymes were restored, as well as morphological absence of peroxisomes. These findings are useful for basic studies on gene therapy of peroxisomal disorders in the cultured cellular system. Further study on expression of human PMP70 cDNA in fibroblasts from Roscher`s group 1 will be also necessary to confirm whether the PMP70 is responsible for Zellweger syndrome.

Authors:
; ;  [1]
  1. Univ. School of Medicine (Japan); and others
Publication Date:
OSTI Identifier:
133975
Report Number(s):
CONF-941009-
Journal ID: AJHGAG; ISSN 0002-9297; TRN: 95:005313-0710
Resource Type:
Journal Article
Journal Name:
American Journal of Human Genetics
Additional Journal Information:
Journal Volume: 55; Journal Issue: Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; PATIENTS; HEREDITARY DISEASES; METABOLIC DISEASES; MORTALITY; GENES; GENE MUTATIONS; LETHAL MUTATIONS; FIBROBLASTS; BIOCHEMISTRY; CELL CONSTITUENTS; RECESSIVE MUTATIONS; ENZYMES

Citation Formats

Shimozawa, N, Suzuki, Y, and Oril, T. The correction of biochemical abnormalities in fibroblasts of a Zellweger patient by gene expression. United States: N. p., 1994. Web.
Shimozawa, N, Suzuki, Y, & Oril, T. The correction of biochemical abnormalities in fibroblasts of a Zellweger patient by gene expression. United States.
Shimozawa, N, Suzuki, Y, and Oril, T. 1994. "The correction of biochemical abnormalities in fibroblasts of a Zellweger patient by gene expression". United States.
@article{osti_133975,
title = {The correction of biochemical abnormalities in fibroblasts of a Zellweger patient by gene expression},
author = {Shimozawa, N and Suzuki, Y and Oril, T},
abstractNote = {Zellweger syndrome is a prototype of peroxisome-deficient disorders and a fatal autosomal recessive disease with no effective therapy. We identified nine genetic complementation groups of these disorders among several laboratories, and mutations in peroxisome assembly factor-1 (PAF-1) and the 70-kDa peroxisomal membrane protein (PMP70) genes have been described in Zellweger patients from our group F and Roscher`s group 1, respectively. We now succeed the permanent recovery of generalized peroxisomal abnormalities in fibroblasts of a Zellweger patient from the group F by the stable transfection of human cDNA encoding PAF-1. In the transfectants, a number of peroxisomal dysfunctions such as lignocelic acid oxidation, dihydroxyacetone phosphate acyltransferase activity and biogenesis of peroxisomal {beta}-oxidation enzymes were restored, as well as morphological absence of peroxisomes. These findings are useful for basic studies on gene therapy of peroxisomal disorders in the cultured cellular system. Further study on expression of human PMP70 cDNA in fibroblasts from Roscher`s group 1 will be also necessary to confirm whether the PMP70 is responsible for Zellweger syndrome.},
doi = {},
url = {https://www.osti.gov/biblio/133975}, journal = {American Journal of Human Genetics},
number = Suppl.3,
volume = 55,
place = {United States},
year = {Thu Sep 01 00:00:00 EDT 1994},
month = {Thu Sep 01 00:00:00 EDT 1994}
}