p53 inactivation leads to impaired motor synchronization in mice.
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.
Campana
Aline L M
AL
Laboratoire 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
Rondi-Reig
Laure
L
Tobin
Christine
C
Lohof
Ann M
AM
Picquet
Florence
F
Falempin
Maurice
M
Weitzman
Jonathan B
JB
Mariani
Jean
J
D000818:Animals; D052160:Benzothiazoles; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology; D007794:Lameness, Animal / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology*; D018656:Muscle Fibers, Fast-Twitch / Q000473:pathology; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology; D009469:Neuromuscular Junction / Q000473:pathology; D009847:Olivary Nucleus / Q000473:pathology / Q000503:physiopathology; D009924:Organ Culture Techniques; D013844:Thiazoles / Q000494:pharmacology; D014050:Toluene / Q000031:analogs & derivatives* / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D016138:Walking
D052160:Benzothiazoles; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; D014050:Toluene; C121565:pifithrin