TY - JOUR
T1 - Expression and localization of Parkinson's disease-associated leucine-rich repeat kinase 2 in the mouse brain
AU - Higashi, Shinji
AU - Moore, Darren J.
AU - Colebrooke, Rebecca E.
AU - Biskup, Saskia
AU - Dawson, Valina L.
AU - Arai, Heii
AU - Dawson, Ted M.
AU - Emson, Piers C.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
KW - Dardarin
KW - Immunohistochemistry
KW - In situ hybridization
KW - PARK8
KW - Parkinson's disease
KW - Parkinsonism
UR - http://www.scopus.com/inward/record.url?scp=33845796537&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845796537&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2006.04246.x
DO - 10.1111/j.1471-4159.2006.04246.x
M3 - Article
C2 - 17101029
AN - SCOPUS:33845796537
SN - 0022-3042
VL - 100
SP - 368
EP - 381
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 2
ER -