Alterations in lipid metabolism gene expression and abnormal lipid accumulation in fibroblast explants from giant axonal neuropathy patients

Dmitry Goryunov,Ronald Kh Liem,Yinghua Pang,Chang Shu,Conrad L Leung

doi:10.1186/1471-2156-8-6

Dmitry Goryunov, Ronald Kh Liem + Show 3 more

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https://doi.org/10.1186/1471-2156-8-6

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Journal: BMC Genetics	Publication Date: Mar 1, 2007
Citations: 56	License type: cc-by

Affiliation: Columbia University

Abstract

BackgroundGiant axonal neuropathy (GAN) is a hereditary neurological disorder that affects both central and peripheral nerves. The main pathological hallmark of the disease is abnormal accumulations of intermediate filaments (IFs) in giant axons and other cell types. Mutations in the GAN gene, encoding gigaxonin, cause the disease. Gigaxonin is important in controlling protein degradation via the ubiquitin-proteasome system. The goal of this study was to examine global alterations in gene expression in fibroblasts derived from newly identified GAN families compared with normal cells.ResultsWe report the characterization of fibroblast explants obtained from two unrelated GAN patients. We identify three novel putative mutant GAN alleles and show aggregation of vimentin IFs in these fibroblasts. By microarray analysis, we also demonstrate that the expression of lipid metabolism genes of the GAN fibroblasts is disrupted, which may account for the abnormal accumulations of lipid droplets in these cells.ConclusionOur findings suggest that aberrant lipid metabolism in GAN patients may contribute to the progression of the disease.

Highlights

Giant axonal neuropathy (GAN) is a hereditary neurological disorder that affects both central and peripheral nerves
We found that the expression of lipid metabolism genes was perturbed in GAN fibroblasts most dramatically
Genotyping of fibroblast explants Four subcutaneous fibroblasts explants, MCH068, MCH070, WG0321 and WG0791, were obtained from the repository for mutant human cell strains at the McGill University Health Center

Summary

Introduction

Giant axonal neuropathy (GAN) is a hereditary neurological disorder that affects both central and peripheral nerves. The main pathological hallmark of the disease is abnormal accumulations of intermediate filaments (IFs) in giant axons and other cell types. Mutations in the GAN gene, encoding gigaxonin, cause the disease. The goal of this study was to examine global alterations in gene expression in fibroblasts derived from newly identified GAN families compared with normal cells. Giant Axonal Neuropathy (GAN) is a severe autosomal recessive disorder that affects both the central and peripheral nervous systems. The most prominent pathological feature of GAN is the large, focal accumulations of neuronal intermediate filaments (IFs) in distended axons [1]. A generalized disorganization of IFs has been proposed to be responsible for GAN [3]

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