Anatomical localization of leucine-rich repeat kinase 2 in mouse brain.
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.
Melrose
H
H
Department of Neuroscience, Genetics of Parkinsonism and Related Disorders, Morris K. Udall Parkinson's Disease Research Center of Excellence, Birdsall Building, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. melrose.heather@mayo.edu
Lincoln
S
S
Tyndall
G
G
Dickson
D
D
Farrer
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D017403:In Situ Hybridization; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D051379:Mice; D010300:Parkinson Disease / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; C495279:Lrrk2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D004298:Dopamine