Elsevier

Neuroscience

Volume 139, Issue 3, 2006, Pages 791-794
Neuroscience

Rapid report
Anatomical localization of leucine-rich repeat kinase 2 in mouse brain

https://doi.org/10.1016/j.neuroscience.2006.01.017Get rights and content

Abstract

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.

Section snippets

Tissue

All animal procedures were approved by the Mayo Clinic Institutional Animal Care and Use Committee (IACUC) and were in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23) revised 1996. Every effort was made to minimize the number of animals used and their suffering.

Four adult FVB/N mice (Taconic, Germantown, NY, USA) were killed and brains were excised rapidly. Half the brain was frozen on dry ice for sagittal

Results

The anatomical localization of mRNA hybridization signal was identical for each of the five probes tested, thus confirming the specificity of the oligonucleotides to the target LRRK2 mRNA sequence (see Fig. 1 for a comparison between LRRK2 exon 10/11 and exon 15 signal). The competition control hybridizations for each probe yielded no signal (see Fig. 2). LRRK2 mRNA signal intensity was always found to be highest in the striatum and the olfactory tubercle (Fig. 2). In addition, robust signal

Discussion

In this study we find that in mouse brain, LRRK2 mRNA is most highly expressed in the striatum, olfactory tubercle and the cortex, which are key regions involved in dopaminergic transmission. The nigrostriatal pathway projects from the dopamine-synthesizing neurons of the substantia nigra pars compacta to striatum. Involved in motor control, it is this pathway that degenerates in PD (reviewed by Vallone et al., 2000). The mesolimbic dopaminergic pathway originates in the midbrain ventral

Acknowledgments

This work was supported by the Parkinson’s Disease Foundation (fellowship award to H.M.) and the Morris. K. Udall Parkinson’s Disease Centre of Excellence.

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