Differential expression of the parkin gene in the human brain and peripheral leukocytes

被引:42
作者
Sunada, Y [1 ]
Saito, F [1 ]
Matsumura, K [1 ]
Shimizu, T [1 ]
机构
[1] Teikyo Univ, Sch Med, Dept Neurol & Neurosci, Itabashi Ku, Tokyo 1738605, Japan
关键词
Parkinson's disease; autosomal recessive juvenile parkinsonism; parkin; alternative splicing; alpha-synuclein; deletion;
D O I
10.1016/S0304-3940(98)00697-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Molecular cloning of the responsible gene on chromosome 6q25.2-27 for autosomal recessive juvenile parkinsonism (AR-JP) identified a novel protein of unknown function, named parkin. In patients with AR-JP, deletions most commonly involve exons 3-5 in the parkin gene. For mutation screening we tried to analyze the parkin transcript amplified by RT-PCR. Based on the assumption that illegitimate transcription of the parkin gene may occur in every cell type, we successfully amplified the parkin message from human peripheral leukocytes using RT-PCR. The parkin transcript in leukocytes was smaller in size than the full-length transcript in the brain. DNA sequencing determined that exons 3-5 were spliced out in the normal human leukocyte transcript. Our results demonstrate that alternative splicing produces distinct parkin transcripts in different tissues. Moreover, physiological splicing of deletion-prone exons may provide an important clue to understanding the pathogenesis of AR-JP. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:180 / 182
页数:3
相关论文
共 11 条
[1]   ILLEGITIMATE TRANSCRIPTION - APPLICATION TO THE ANALYSIS OF TRUNCATED TRANSCRIPTS OF THE DYSTROPHIN GENE IN NONMUSCLE CULTURED-CELLS FROM DUCHENNE AND BECKER PATIENTS [J].
CHELLY, J ;
GILGENKRANTZ, H ;
HUGNOT, JP ;
HAMARD, G ;
LAMBERT, M ;
RECAN, D ;
AKLI, S ;
COMETTO, M ;
KAHN, A ;
KAPLAN, JC .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 88 (04) :1161-1166
[2]   Prevalence of Parkinson's disease in the elderly: The Rotterdam study [J].
deRijk, MC ;
Breteler, MMB ;
Graveland, GA ;
Ott, A ;
Grobbee, DE ;
vanderMeche, FGA ;
Hofman, A .
NEUROLOGY, 1995, 45 (12) :2143-2146
[3]   A susceptibility locus for Parkinson's disease maps to chromosome 2p13 [J].
Gasser, T ;
Müller-Myhsok, B ;
Wszolek, ZK ;
Oehlmann, R ;
Calne, DB ;
Bonifati, V ;
Bereznai, B ;
Fabrizio, E ;
Vieregge, P ;
Horstmann, RD .
NATURE GENETICS, 1998, 18 (03) :262-265
[4]  
HATTORI N, 1998, IN PRESS ANN NEUROL
[5]   Clinical analysis of 17 patients in 12 Japanese families with autosomal-recessive type juvenile parkinsonism [J].
Ishikawa, A ;
Tsuji, S .
NEUROLOGY, 1996, 47 (01) :160-166
[6]   Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism [J].
Kitada, T ;
Asakawa, S ;
Hattori, N ;
Matsumine, H ;
Yamamura, Y ;
Minoshima, S ;
Yokochi, M ;
Mizuno, Y ;
Shimizu, N .
NATURE, 1998, 392 (6676) :605-608
[7]   Ala30Pro mutation in the gene encoding α-synuclein in Parkinson's disease [J].
Krüger, R ;
Kuhn, W ;
Müller, T ;
Woitalla, D ;
Graeber, M ;
Kösel, S ;
Przuntek, H ;
Epplen, JT ;
Schöls, L ;
Riess, O .
NATURE GENETICS, 1998, 18 (02) :106-108
[8]   A CLINICAL GENETIC-STUDY OF PARKINSONS-DISEASE - EVIDENCE FOR DOMINANT TRANSMISSION [J].
LAZZARINI, AM ;
MYERS, RH ;
ZIMMERMAN, TR ;
MARK, MH ;
GOLBE, LI ;
SAGE, JI ;
JOHNSON, WG ;
DUVOISIN, RC .
NEUROLOGY, 1994, 44 (03) :499-506
[9]  
Matsumine H, 1997, AM J HUM GENET, V60, P588
[10]   Mutation in the alpha-synuclein gene identified in families with Parkinson's disease [J].
Polymeropoulos, MH ;
Lavedan, C ;
Leroy, E ;
Ide, SE ;
Dehejia, A ;
Dutra, A ;
Pike, B ;
Root, H ;
Rubenstein, J ;
Boyer, R ;
Stenroos, ES ;
Chandrasekharappa, S ;
Athanassiadou, A ;
Papapetropoulos, T ;
Johnson, WG ;
Lazzarini, AM ;
Duvoisin, RC ;
DiIorio, G ;
Golbe, LI ;
Nussbaum, RL .
SCIENCE, 1997, 276 (5321) :2045-2047