Expression and localization of Parkinson's disease-associated leucine-rich repeat kinase 2 in the mouse brain

• Published in: Journal of neurochemistry 2007-01, Vol.100 (2), p.368-381
• Main Authors: Higashi, Shinji, Moore, Darren J, Colebrooke, Rebecca E, Biskup, Saskia, Dawson, Valina L, Arai, Heii, Dawson, Ted M, Emson, Piers C
• Format: Article
• Language: English
• Subjects: Animals; Biogenic Monoamines - metabolism; Biological and medical sciences; Brain; Brain - anatomy & histology; Brain - metabolism; Cell Count - methods; dardarin; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Gene expression; Gene Expression - physiology; Green Fluorescent Proteins - biosynthesis; immunohistochemistry; Immunohistochemistry - methods; in situ hybridization; In Situ Hybridization - methods; Kinases; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Medical sciences; Mice; Mice, Mutant Strains; Mutation; Nerve Tissue Proteins - metabolism; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; PARK8; Parkinson's disease; parkinsonism; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - metabolism; Rodents; Vesicular Monoamine Transport Proteins - genetics
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.04246.x

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.