RT info:eu-repo/semantics/article
T1 Behavioral, neurochemical, and pathologic alterations in bacterial artificial chromosome transgenic G2019S leucine-rich repeated kinase 2 rats
A1 Lee, Jang-Won
A1 Tapias, Victor
A1 Di Maio, Roberto
A1 Greenamyre, J. Timothy
A1 Cannon, Jason R.
AB Mutations in leucine-rich repeated kinase 2 (LRRK2) cause autosomal dominant late-onset Parkinson's disease (PD), and the G2019S mutation in the kinase domain of LRRK2 is the most common genetic cause of familial PD. Enhanced kinase activity of G2019S LRRK2 is a suspected mechanism for carriers to develop PD but pathophysiological function of G2019S LRRK2 is not clear. The objective of the present study was to characterize a bacterial artificial chromosome rat expressing human G2019S LRRK2. Immunoblotting analysis showed that G2019S LRRK2 expression was approximately 5-8 times higher than wild-type rat LRRK2. At ages of 4, 8, and 12 months, our characterization showed that expression of G2019S LRRK2 induced oxidative stress in striatum and substantia nigra, increased inducible nitric oxide synthase expression in nigral dopamine neurons, and abnormal morphology of nigral dopaminergic neurons in transgenic rats compared with wild-type, without inducing overt neurodegeneration in nigrostriatal dopaminergic neurons. Thus, we conclude that although this model does not reproduce the key features of end-stage PD, important preclinical features of the disease are evident, which may be useful in studying the earliest stages of PD and for gene-environment interaction studies.
SN 0197-4580
YR 2015
FD 2015
LK https://uvadoc.uva.es/handle/10324/63882
UL https://uvadoc.uva.es/handle/10324/63882
LA eng
NO Neurobiology of Aging, Enero 2015, vol. 36, n. 1. p. 505-518
NO Producción Científica
DS UVaDOC
RD 08-ago-2024