Microarray expression analysis of gad mice implicates involvement of Parkinson's disease associated UCH-L1 in multiple metabolic pathways.
Parkinson's disease (PD) is thought to be caused by environmental and genetic factors. Mutations in four genes, alpha-synuclein, parkin, DJ-1, and UCH-L1, have been identified in autosomal inherited forms of PD. The pathogenetic cause for the loss of neuronal cells in PD patients, however, remains to be determined. Due to the rarity of mutations in humans with PD, the analysis of animal models might help to further gain insights into the pathogenesis of familial PD. For UCH-L1, deficiency has been described in gad mice leading to axonal degeneration and formation of spheroid bodies in nerve terminals. Here, we investigated the gene expression pattern of the brain of 3-month-old Uch-l1-deficient gracile axonal dystrophy (gad) mice by microarray analysis. A total of 146 genes were differentially regulated by at least a 1.4-fold change with 103 being up-regulated and 43 being down-regulated compared with age and sex matched wildtype littermate mice. The gene products with altered expression are involved in protein degradation, cell cycle, vesicle transport, cellular structure, signal transduction, and transcription regulation. Most of the genes were modestly regulated, which is in agreement that severe alteration of these pathways might be lethal. Among the genes most significantly down-regulated is the brain-derived neurotrophic factor which might be one aspect of the pathogenesis in gad mice. Interestingly, several subunits of the transcription factor CCAAT/enhancer binding protein are up-regulated, which plays a central role in most altered pathways.
Bonin
M
M
Department of Medical Genetics, University of Tübingen, Calwerstrasse 7, 72076 Tübingen, Germany.
Poths
S
S
Osaka
H
H
Wang
Y-L
YL
Wada
K
K
Riess
O
O
D000818:Animals; D001921:Brain / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; D043222:Ubiquitin Thiolesterase; C496976:Uchl1 protein, mouse