Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease.
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.
Li
Yanping
Y
Department of Neurology and Neurosciences, Weill Medical College of Cornell University, New York, New York, USA.
Liu
Wencheng
W
Oo
Tinmarla F
TF
Wang
Lei
L
Tang
Yi
Y
Jackson-Lewis
Vernice
V
Zhou
Chun
C
Geghman
Kindiya
K
Bogdanov
Mikhail
M
Przedborski
Serge
S
Beal
M Flint
MF
Burke
Robert E
RE
Li
Chenjian
C
D000367:Age Factors; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001058:Apomorphine / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D022202:Chromosomes, Artificial, Bacterial; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D018014:Gene Transfer Techniques; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D007980:Levodopa / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D009069:Movement Disorders / Q000188:drug therapy / Q000235:genetics; D020125:Mutation, Missense; D009474:Neurons / Q000473:pathology / Q000502:physiology; D009627:Nomifensine / Q000494:pharmacology; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
D000978:Antiparkinson Agents; D018765:Dopamine Uptake Inhibitors; D009627:Nomifensine; D007980:Levodopa; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D001058:Apomorphine; D004298:Dopamine