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Tet-Off Conditional Transgenic Approaches in Modeling Parkinson's Disease in Mice
Yunjong Lee1,*
1Institute for cell engineering and Department of Physiology, Johns Hopkins University School of Medicine
*Corresponding author
  Received : April 28, 2010
  Published : April 30, 2010
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Parkinson's disease (PD) is the most common movement disorder in which a progressive neurodegeneration in the substantia nigra pars compacta (SNpc) of the midbrain is responsible for most of clinical symptoms of the disease. Although most cases of PD have unknown etiology, there are rare forms of inherited PD. The identification of PD-causing mutations in dominantly inherited (α-synuclein and LRRK2) and recessively inherited genes (parkin, PINK1 and DJ-1) has provided the basis for the studies on the molecular pathways by which the dopaminergic (DA) neuronal death occurs in PD as well as for generating PD animal models. However, there are no mouse models which can successfully reproduce the major characteristics of PD, including a progressive DA neurodegeneration, motor deficits and inclusion body formation, despite the rigorous attempts to produce PD mouse models expressing PD causing genes such as α-synuclein, LRRK2 and their variants. Even the degeneration of DA neurons in the midbrain cannot be phenocopied in any of the mouse models reported so far, thus hampering the studies regarding cell death pathways in vivo. Tet-off conditional genetic switch has been widely used to express certain genes in selected organs. The ability to turn on and off the gene expression with tetracycline has enabled this system to be suitable for generating transgenic animals expressing potentially toxic proteins. The robust induction of transgene and pharmacological control of transgene expression is central for the Tet-off transgenic approach to improve the previously developed conventional PD animal models. In this review, the partial success and limitations of previously reported conventional PD mouse models will be discussed with the main focus on the ways to enhance the pathological phenotypes of the mouse models. In addition, the principles of Tet-off transgenic techniques will be presented and reviewed regarding its potential application in successfully modeling the disease in mice.

Keyword: Parkinson's disease, tet-off genetic switch, transgenesis, PD mouse model, tetracycline responsive transcription activator, tet promoter, tTA, tetP
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