Dopaminergic Loss and Inclusion Body Formation in 
-Synuclein Mice: Implications for Neurodegenerative Disorders
Eliezer Masliah,
12*
Edward Rockenstein,
1
Isaac Veinbergs,
2
Margaret Mallory,
1
Makoto Hashimoto,
1
Ayako Takeda,
13
Yutaka Sagara,
2
Abbyann Sisk,
2
Lennart Mucke
4
To elucidate the role of the synaptic protein 
-synuclein in
neurodegenerative disorders, transgenic mice expressing wild-type human
-synuclein were generated. Neuronal expression of human -synuclein resulted in progressive accumulation of
-synuclein--and ubiquitin-immunoreactive inclusions in neurons in
the neocortex, hippocampus, and substantia nigra. Ultrastructural
analysis revealed both electron-dense intranuclear deposits and
cytoplasmic inclusions. These alterations were associated with loss of
dopaminergic terminals in the basal ganglia and with motor impairments.
These results suggest that accumulation of wild-type -synuclein may
play a causal role in Parkinson's disease and related conditions.
1 Department of Neurosciences,
2 Department of Pathology, University of California
San Diego, La Jolla, CA 92093-0624, USA.
3 Department of Psychiatry, Yokohama City
University, School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236, Japan.
4 Gladstone Institute of Neurological Disease
and Department of Neurology, University of California San Francisco,
Post Office Box 419100, San Francisco, CA 94141-9100, USA.
*
To whom correspondence should be addressed. E-mail:
emasliah{at}ucsd.edu
