cubes

Abstract

Phenotypic characterization of a genetically modified animal model of Parkinson’s Disease

S RAMBOZ1, K CIRILLO1, R SPRINGER1, M MAZZELLA, D HAVAS1, K WALKER1, J.A. SANCHEZ-PADILLA1, G TOMBAUGH1, A GHAVAMI1.
1PsychoGenics, Tarrytown, NY, USA

PsychoGenics, Inc has acquired a license for a genetically modified α-synuclein mouse line expressing the human wild-type α-synuclein under the murine Thy-1 promoter (Line 61). This transgenic line has been reported to display pathological features of Parkinson’s disease patients including impaired motor and cognitive deficits, α-synuclein aggregates, and accumulation of phosphorylated α-synuclein in striatum and substantia nigra pars compacta (SNc). For the past year, we have conducted a longitudinal phenotypic profiling of Line 61 using a combination of behavior, in situ analysis of catecholamines, immunohistochemistry, and brain slice electrophysiology. Our data confirm previous published data and demonstrate earlier motor impairment onset. In addition using brain slice electrophysiology, we analyzed spontaneous miniature excitatory postsynaptic currents (mEPSCs) in spiny projection neurons (SPNs) in the dorsal striatum and confirmed a decrease in the frequency but not amplitude of mEPSCs in 6-month old Line 61 mice.

 

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