REVIEW

Transcription factor Pitx3 mutant mice as a model for Parkinson’s disease

  • Fu-Ming Zhou , 1 ,
  • Li Li 1 ,
  • Juming Yue 2 ,
  • John A. Dani 3
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  • 1. Department of Pharmacology, University of Tennessee College of Medicine, Memphis, TN 38103, USA
  • 2. Department of Pathology, University of Tennessee College of Medicine, Memphis, TN 38103, USA
  • 3. Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

Received date: 15 Aug 2016

Accepted date: 20 Oct 2016

Published date: 26 Dec 2016

Copyright

2016 Higher Education Press and Springer-Verlag Berlin Heidelberg

Abstract

BACKGROUND: Parkinsonʼs disease (PD) is a common, age-dependent degenerative neurological disorder impairing motor control function and cognition. A key pathology of PD is a degeneration of the nigrostriatal dopamine system, leading to a severe dopamine denervation in the striatum and dynsfunction of the striatal neural circuits.

OBJECTIVE: To better understand the pathophysiology of the nigrostriatal dopamine denervation and to discover better treatments, animal PD models are needed.

METHODS: The authors’ original research on the transcription factor Pitx3 null mutant mice and the relevant literature were reviewed.

RESULTS: An important feature of an animal PD model is the severe, PD-like nigrostriatal dopamine denervation. This feature is provided in the transcription factor Pitx3 null mutant mice. These mice have a severe and bilateral nigral dopamine neuron loss and dopamine denervation in the dorsal striatum, while the dopamine neuron loss in the ventral tegmental area and dopamine denervation in the ventral striatum are moderate, creating a dorsal-ventral dopamine loss gradient and mimicking the dopamine denervation pattern in PD. Pitx3 null mice show motor function deficits in the balance beam and pole tests and these deficits are reversed by L-3,4-dihydroxyphenylalanine (L-dopa). These mice also show impaired cognitive functions as indicated by reduced motor learning and avoidance memory. L-dopa, D1 agonists and, to a lesser extent, D2 agonists, induce normal horizontal movements (walking) and also dyskinesia-like movements consisting of vertical body trunk movements and waving paw movements.

CONCLUSIONS: The easy-to-maintain Pitx3 null mice with an autogenic, consistent and gradient dopamine denervation are a convenient and suitable mouse model to study the consequences of dopamine loss in PD and to test dopaminergic replacement therapies for PD.

Cite this article

Fu-Ming Zhou , Li Li , Juming Yue , John A. Dani . Transcription factor Pitx3 mutant mice as a model for Parkinson’s disease[J]. Frontiers in Biology, 2016 , 11(6) : 427 -438 . DOI: 10.1007/s11515-016-1429-8

Acknowledgements

This work was supported by NIH grants R01NS097671 and R03NS085380 to FMZ and R01NS21229 and R01DA09411 to JAD.

Compliance with ethics guidelines

Fu-Ming Zhou, Li Li, Juming Yue, John A. Dani declare that they have no conflict of interest. This article is a literature review.
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