Anatomical localization of Leucine-rich repeat kinase 2 in mouse brain

被引:102
作者
Melrose, H
Lincoln, S
Tyndall, G
Dickson, D
Farrer, M
机构
[1] Mayo Clin, Dept Neurosci Genet Parkinsonism & Related Disord, Morris K Udall Parkinsons Dis Res Ctr Excellence, Jacksonville, FL 32224 USA
[2] Mayo Clin, Morris K Udall Parkinsons Dis Res Ctr Excellence, Dept Pathol Genet Parkinsonism & Related Disorder, Jacksonville, FL 32224 USA
关键词
Parkinson's disease; in situ hybridization; RT-PCR; basal ganglia; mRNA expression;
D O I
10.1016/j.neuroscience.2006.01.017
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Mutations in, leucine-rich repeat kinase 2 (LRRK2) have recently been identified in autosomal dominant late-onset Parkinson's disease. Expression of LRRK2 has previously been reported in brain; however, no precise anatomical information is yet available. We have performed in situ hybridization and quantitative reverse transcription polymerase chain reaction to map LRRK2 mRNA expression in mouse brain. We find LRRK2 is highly expressed in the striatum, cortex and olfactory tubercle; however, little or no expression is found in the substantia nigra, where dopaminergic neurons preferentially degenerate in Parkinson's disease. These findings suggest that LRRK2 mRNA is expressed in dopamine-receptive areas rather than in the dopamine-synthesizing neurons. Consistent with a role LRRK2 in Parkinson's disease, dysfunction of leucine-rich repeat kinase 2 protein in dopamine-innervated areas may to lead to altered dopaminergic neurotransmission and degeneration of the nigro-striatal pathway. (c) 2006 Published by Elsevier Ltd on behalf of IBRO.
引用
收藏
页码:791 / 794
页数:4
相关论文
共 11 条
  • [1] NEUROTENSIN INCREASES TYROSINE-HYDROXYLASE MESSENGER RNA-POSITIVE NEURONS IN SUBSTANTIA-NIGRA AFTER RETROGRADE AXONAL-TRANSPORT
    BURGEVIN, MC
    CASTEL, MN
    QUARTERONET, D
    CHEVET, T
    LADURON, PM
    [J]. NEUROSCIENCE, 1992, 49 (03) : 627 - 633
  • [2] RETROGRADE AXONAL-TRANSPORT OF NEUROTENSIN IN THE DOPAMINERGIC NIGROSTRIATAL PATHWAY IN THE RAT
    CASTEL, MN
    MALGOURIS, C
    BLANCHARD, JC
    LADURON, PM
    [J]. NEUROSCIENCE, 1990, 36 (02) : 425 - 430
  • [3] LRRK2 mutations in Parkinson disease
    Farrer, M
    Stone, J
    Mata, IF
    Lincoln, S
    Kachergus, J
    Hulihan, M
    Strain, KJ
    Maraganore, DM
    [J]. NEUROLOGY, 2005, 65 (05) : 738 - 740
  • [4] The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity
    Gloeckner, CJ
    Kinkl, N
    Schumacher, A
    Braun, RJ
    O'Neill, E
    Meitinger, T
    Kolch, W
    Prokisch, H
    Ueffing, M
    [J]. HUMAN MOLECULAR GENETICS, 2006, 15 (02) : 223 - 232
  • [5] Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism:: Evidence of a common founder across European populations
    Kachergus, J
    Mata, IF
    Hulihan, M
    Taylor, JP
    Lincoln, S
    Aasly, J
    Gibson, JM
    Ross, OA
    Lynch, T
    Wiley, J
    Payami, H
    Nutt, J
    Maraganore, DM
    Czyzewski, K
    Styczynska, M
    Wszolek, ZK
    Farrer, MJ
    Toft, M
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2005, 76 (04) : 672 - 680
  • [6] LRRK2 R1441G in Spanish patients with Parkinson's disease
    Mata, IF
    Taylor, JP
    Kachergus, J
    Hulihan, M
    Huerta, C
    Lahoz, C
    Blazquez, M
    Guisasola, LM
    Salvador, C
    Ribacoba, R
    Martinez, C
    Farrer, M
    Alvarez, V
    [J]. NEUROSCIENCE LETTERS, 2005, 382 (03) : 309 - 311
  • [7] Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease
    Paisán-Ruíz, C
    Jain, S
    Evans, EW
    Gilks, WP
    Simón, J
    van der Brug, M
    de Munain, AL
    Aparicio, S
    Gil, AM
    Khan, N
    Johnson, J
    Martinez, JR
    Nicholl, D
    Carrera, IM
    Pena, AS
    de Silva, R
    Lees, A
    Martí-Massó, JF
    Pérez-Tur, J
    Wood, NW
    Singleton, AB
    [J]. NEURON, 2004, 44 (04) : 595 - 600
  • [8] Molecular mechanisms regulating the retrograde axonal transport of neurotrophins
    Reynolds, AJ
    Bartlett, SE
    Hendry, IA
    [J]. BRAIN RESEARCH REVIEWS, 2000, 33 (2-3) : 169 - 178
  • [9] Structure and function of dopamine receptors
    Vallone, D
    Picetti, R
    Borrelli, E
    [J]. NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, 2000, 24 (01) : 125 - 132
  • [10] Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity
    West, AB
    Moore, DJ
    Biskup, S
    Bugayenko, A
    Smith, WW
    Ross, CA
    Dawson, VL
    Dawson, TM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (46) : 16842 - 16847