Non-motor and motor features in LRRK2 transgenic mice.
BACKGROUND
Non-motor symptoms are increasingly recognized as important features of Parkinson's disease (PD). LRRK2 mutations are common causes of familial and sporadic PD. Non-motor features have not been yet comprehensively evaluated in LRRK2 transgenic mouse models.


OBJECTIVE
Using a transgenic mouse model overexpressing the R1441G mutation of the human LRRK2 gene, we have investigated the longitudinal correlation between motor and non-motor symptoms and determined if specific non-motor phenotypes precede motor symptoms.


METHODS
We investigated the onset of motor and non-motor phenotypes on the LRRK2(R1441G) BAC transgenic mice and their littermate controls from 4 to 21 month-old using a battery of behavioral tests. The transgenic mutant mice displayed mild hypokinesia in the open field from 16 months old, with gastrointestinal dysfunctions beginning at 6 months old. Non-motor features such as depression and anxiety-like behaviors, sensorial functions (pain sensitivity and olfaction), and learning and memory abilities in the passive avoidance test were similar in the transgenic animals compared to littermate controls.


CONCLUSIONS
LRRK2(R1441G) BAC transgenic mice displayed gastrointestinal dysfunction at an early stage but did not have abnormalities in fine behaviors, olfaction, pain sensitivity, mood disorders and learning and memory compared to non-transgenic littermate controls. The observations on olfaction and gastrointestinal dysfunction in this model validate findings in human carriers. These mice did recapitulate mild Parkinsonian motor features at late stages but compensatory mechanisms modulating the progression of PD in these models should be further evaluated.
Behavioral Neuroscience Laboratory, National Neuroscience Institute, Singapore, Singapore. zoe.bichler@gmail.com
Zoë
Z
Bichler
Han Chi
HC
Lim
Li
L
Zeng
Eng King
EK
Tan
D000367:Age Factors; D000818:Animals; D001007:Anxiety / Q000235:genetics; D001522:Behavior, Animal; D003863:Depression / Q000235:genetics; D004195:Disease Models, Animal; D005767:Gastrointestinal Diseases / Q000235:genetics / Q000503:physiopathology; D015870:Gene Expression; D007858:Learning; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics*; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; C495279:Lrrk2 protein, mouse; D017346:Protein Serine-Threonine Kinases