A comparative analysis of leucine-rich repeat kinase 2 (Lrrk2) expression in mouse brain and Lewy body disease.
Pathogenic substitutions in leucine-rich repeat kinase 2 (LRRK2, Lrrk2) have been genetically linked to familial, late-onset Parkinsonism. End-stage disease is predominantly associated with nigral neuronal loss and Lewy body pathology, but patients may have gliosis, tau or ubiquitin inclusions (pleomorphic pathology). The anatomical distribution of Lrrk2 protein may provide insight into its function in health and neurodegeneration, thus we performed a comparative study with 'in-house' and commercially available Lrrk2 antibodies using brain tissue from wild type and human Lrrk2 transgenic bacterial artificial chromosome (BAC) mice, and from diffuse Lewy body disease (DLBD) patients. Lrrk2 protein was ubiquitously expressed and relatively abundant in most brain regions, including the substantia nigra, thalamus and striatum. Lrrk2 was not a major component of Lewy body or neuritic pathology associated with Parkinson's disease. However, selective loss of dopaminergic neurons in Lrrk2-associated Parkinsonism argues the protein may have regional-specific interactions. Lrrk2 immunohistochemical staining was present in the subventricular zone, a region containing stem cells that give rise to both neurons and glia. A role for Lrrk2 in neurogenesis might provide further insight into the aberrant role of mutant protein in age-associated neurodegeneration with pleomorphic pathology.
Melrose
H L
HL
Molecular Genetics Laboratory and Core, Morris K. Udall Parkinson's Disease Research Center of Excellence, Mayo Clinic, Department of Neuroscience, 4500 San Pablo Road, Jacksonville, FL 32224, USA. Melrose.heather@mayo.edu
Kent
C B
CB
Taylor
J P
JP
Dachsel
J C
JC
Hinkle
K M
KM
Lincoln
S J
SJ
Mok
S S
SS
Culvenor
J G
JG
Masters
C L
CL
Tyndall
G M
GM
Bass
D I
DI
Ahmed
Z
Z
Andorfer
C A
CA
Ross
O A
OA
Wszolek
Z K
ZK
Delldonne
A
A
Dickson
D W
DW
Farrer
M J
MJ
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D002461:Cell Line, Transformed; D022202:Chromosomes, Artificial, Bacterial / Q000502:physiology; D015870:Gene Expression / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; C485184:enhanced green fluorescent protein; C103469:polysialyl neural cell adhesion molecule; D049452:Green Fluorescent Proteins; D014446:Tyrosine 3-Monooxygenase; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases