Mutant LRRK2R1441G BAC transgenic mice recapitulate cardinal features of Parkinson's disease

被引：403

作者：

Li, Yanping ^{[1
]}

Liu, Wencheng ^{[1
]}

Oo, Tinmarla F. ^{[2
,3
]}

Wang, Lei ^{[1
,4
]}

Tang, Yi ^{[1
]}

Jackson-Lewis, Vernice ^{[2
,3
]}

Zhou, Chun ^{[2
,3
]}

Geghman, Kindiya ^{[1
]}

Bogdanov, Mikhail ^{[1
,4
]}

Przedborski, Serge ^{[2
,3
]}

Beal, M. Flint ^{[1
]}

Burke, Robert E. ^{[2
,3
]}

Li, Chenjian ^{[1
]}

机构：

[1] Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA

[2] Columbia Univ, Dept Neurol, New York, NY USA

[3] Columbia Univ, Dept Pathol, New York, NY USA

[4] Bedford Vet Adm Med Ctr, Bedford, MA USA

来源：

NATURE NEUROSCIENCE | 2009年 / 12卷 / 07期

基金：

美国国家卫生研究院;

关键词：

MUTATION; GENE; ACTIVATION; EXPRESSION; PATHOLOGY; REGION;

D O I：

10.1038/nn.2349

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) are the most common genetic cause of Parkinson's disease. We created a LRRK2 transgenic mouse model that recapitulates cardinal features of the disease: an age-dependent and levodopa-responsive slowness of movement associated with diminished dopamine release and axonal pathology of nigrostriatal dopaminergic projection. These mice provide a valid model of Parkinson's disease and are a resource for the investigation of pathogenesis and therapeutics.

引用

页码：826 / 828

页数：3

共 15 条

[11] Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease [J].

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 .

NEURON, 2004, 44 (04) :595-600

[12] 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

[13] Increased frequency of the LRRK2 G2019S mutation in an elderly Ashkenazi Jewish population is not associated with dementia [J].

Saunders-Pullman, Rachel ;

Lipton, Richard B. ;

Senthil, Geetha ;

Katz, Mindy ;

Costan-Toth, Camille ;

Derby, Carol ;

Bressman, Susan ;

Verghese, Joe ;

Ozelius, Laurie J. .

NEUROSCIENCE LETTERS, 2006, 402 (1-2) :92-96

[14] Haplotypes and gene expression implicate the MAPT region for Parkinson disease -: The GenePD Study [J].

Tobin, J. E. ;

Latourelle, J. C. ;

Lew, M. F. ;

Klein, C. ;

Suchowersky, O. ;

Shill, H. A. ;

Golbe, L. I. ;

Mark, M. H. ;

Growdon, J. H. ;

Wooten, G. F. ;

Racette, B. A. ;

Perlmutter, J. S. ;

Watts, R. ;

Guttman, M. ;

Baker, K. B. ;

Goldwurm, S. ;

Pezzoli, G. ;

Singer, C. ;

Saint-Hilaire, M. H. ;

Hendricks, A. E. ;

Williamson, S. ;

Nagle, M. W. ;

Wilk, J. B. ;

Massood, T. ;

Laramie, J. M. ;

DeStefano, A. L. ;

Litvan, I. ;

Nicholson, G. ;

Corbett, A. ;

Isaacson, S. ;

Burn, D. J. ;

Chinnery, P. F. ;

Pramstaller, P. P. ;

Sherman, S. ;

Al-Hinti, J. ;

Drasby, E. ;

Nance, M. ;

Moller, A. T. ;

Ostergaard, K. ;

Roxburgh, R. ;

Snow, B. ;

Slevin, J. T. ;

Cambi, F. ;

Gusella, J. F. ;

Myers, R. H. .

NEUROLOGY, 2008, 71 (01) :28-34

[15] Mutations in LRRK2 cause autosomal-dominant Parkinsonism with pleomorphic pathology [J].

Zimprich, A ;

Biskup, S ;

Leitner, P ;

Lichtner, P ;

Farrer, M ;

Lincoln, S ;

Kachergus, J ;

Hulihan, M ;

Uitti, RJ ;

Calne, DB ;

Stoessl, AJ ;

Pfeiffer, RF ;

Patenge, N ;

Carbajal, IC ;

Vieregge, P ;

Asmus, F ;

Müller-Myhsok, B ;

Dickson, DW ;

Meitinger, T ;

Strom, TM ;

Wszolek, ZK ;

Gasser, T .

NEURON, 2004, 44 (04) :601-607

← 1 2 →