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p53 inactivation leads to impaired motor synchronization in mice
Aline L M Campana1, Laure Rondi-Reig, Christine Tobin
1Laboratoire Développement et Vieillissement du Système Nerveux, Université P. & M. Curie--CNRS, UMR NPA 7102, case 14, 9 quai Saint Bernard, 75005 Paris, France. aline.campana@snv.jussieu.fr
Abstract:
We have combined genetic and pharmacological approaches to investigate the behavioural consequences of inactivation of the murine p53 protein. Our behavioural analysis revealed that p53-null mice (p53KO) exhibit a very specific and significant motor deficit in rapid walking synchronization. This deficit, observed using the rotarod test, was the only behavioural defect of p53KO mice. We demonstrated that it was not due to an increase in neuronal number or abnormal connectivity in the olivo-cerebellar system, thought to control motor synchronization. In order to test the role of p53 in the central nervous system, we injected a pharmacological inhibitor of p53 activation, pifithrin-alpha, into the cerebellum of wild-type mice. This treatment mimicked the walking synchronization deficit of p53KO mice, suggesting that presence of p53 protein in the cerebellum is necessary to execute this synchronization of walking. Our investigation reveals a functional role of cerebellar p53 protein in adult walking synchronization.
Insights
Mice lacking the p53 protein show a specific motor deficit in walking synchronization. Cerebellar p53 is essential for this motor function in adult mice.
Area of Science:
- Neuroscience
- Genetics
- Motor Control
Background:
- The p53 protein is a critical tumor suppressor.
- Its role in the central nervous system and motor control is not well understood.
Purpose of the Study:
- To investigate the behavioral consequences of p53 protein inactivation in mice.
- To determine the role of p53 in motor synchronization.
Main Methods:
- Genetic inactivation of the p53 protein in mice (p53-null mice).
- Behavioral analysis using the rotarod test for motor synchronization.
- Pharmacological inhibition of p53 activation in the cerebellum of wild-type mice using pifithrin-alpha.
Main Results:
- p53-null mice exhibited a specific and significant deficit in rapid walking synchronization.
- No other behavioral defects were observed in p53-null mice.
- Pharmacological inhibition of p53 in the cerebellum mimicked the motor deficit seen in p53-null mice.
Conclusions:
- Cerebellar p53 protein plays a crucial role in adult walking synchronization.
- The p53 protein's function in the central nervous system extends to motor control.