10.1371/journal.pone.0070249PLoS ONE87-POLN

A Tjolsen

AH Schapira

D Ramonet

DG Healy

DM Crabtree

EH Norris

EK Tan

EM Khedr

Eng King Tan

F Gillardon

G Ren

H Petrovitch

H Vlajinac

Han Chi Lim

HL Melrose

HM Gao

Huaibin Cai

HV Lad

I Branchi

J Peng

J Ruiz-Martinez

J Simon-Sanchez

JF Marti-Masso

JL Tillerson

JS Mogil

KK Johansen

KM Hinkle

KR Chaudhuri

LF Burbulla

Li Zeng

LX Blonder

M Potter

M Poulopoulos

MC Herzig

MC Rodriguez-Oroz

MC Wey

MF Beal

MI Ekstrand

MJ Devine

P Ardayfio

P Desplats

P Martinez-Martin

PN Gandhi

RE Brown

RM Quock

S Zambito Marsala

SC Landis

SJ Royle

SM Fleming

T Li

T Maekawa

TB Sherer

TM Dawson

TN Taylor

U Kumari

V Voikar

W Satake

WG Meissner

WW Smith

X Li

Y Li

Y Tong

Y Wu

Zoë Bichler

PubMed

<div>BackgroundNon-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.ObjectiveUsing 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.MethodologyWe investigated the onset of motor and non-motor phenotypes on the LRRK2R1441G 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.ConclusionsLRRK2R1441G 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.</div

Zoë Bichler (439623)

Han Chi Lim (439624)

Li Zeng (77324)

Eng King Tan (250084)

The Francis Crick Institute

Non-Motor and Motor Features in LRRK2 Transgenic Mice

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.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.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.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

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PLoS ONE

Non-motor and motor features in LRRK2 transgenic mice.

 transgenic mouse models. gene, we have investigated the longitudinal correlation between motor and non-motor symptoms and determined if specific non-motor phenotypes precede motor symptoms. 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. 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

Non-Motor and Motor Features in LRRK2 Transgenic Mice

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