Expression and localization of Parkinson's disease-associated leucine-rich repeat kinase 2 in the mouse brain.
Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) have been identified as the cause of familial Parkinson's disease (PD) at the PARK8 locus. To begin to understand the physiological role of LRRK2 and its involvement in PD, we have investigated the distribution of LRRK2 mRNA and protein in the adult mouse brain. In situ hybridization studies indicate sites of mRNA expression throughout the mouse brain, with highest levels of expression detected in forebrain regions, including the cerebral cortex and striatum, intermediate levels observed in the hippocampus and cerebellum, and low levels in the thalamus, hypothalamus and substantia nigra. Immunohistochemical studies demonstrate localization of LRRK2 protein to neurones in the cerebral cortex and striatum, and to a variety of interneuronal subtypes in these regions. Furthermore, expression of LRRK2 mRNA in the striatum of VMAT2-deficient mice is unaltered relative to wild-type littermate controls despite extensive dopamine depletion in this mouse model of parkinsonism. Collectively, our results demonstrate that LRRK2 is present in anatomical brain regions of direct relevance to the pathogenesis of PD, including the nigrostriatal dopaminergic pathway, in addition to other regions unrelated to PD pathology, and is likely to play an important role in the normal function of telencephalic forebrain neurones and other neuronal populations.
Higashi
Shinji
S
Laboratory of Molecular Neuroscience, The Babraham Institute, Babraham, Cambridge, UK.
Moore
Darren J
DJ
Colebrooke
Rebecca E
RE
Biskup
Saskia
S
Dawson
Valina L
VL
Arai
Heii
H
Dawson
Ted M
TM
Emson
Piers C
PC
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D002452:Cell Count / Q000379:methods; D015870:Gene Expression / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics
D015306:Biogenic Monoamines; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C493453:Slc18a2 protein, mouse; D050493:Vesicular Monoamine Transport Proteins; D049452:Green Fluorescent Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; C495279:Lrrk2 protein, mouse; D017346:Protein Serine-Threonine Kinases