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Altered MAP kinase phosphorylation and impaired motor coordination in PTPRR deficient mice
Author(s) -
Chirivi Renato G. S.,
Noordman Yvet E.,
Zee Catharina E. E. M. Van der,
Hendriks Wiljan J. A. J.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04398.x
Subject(s) - cerebellum , biology , purkinje cell , phosphorylation , microbiology and biotechnology , kinase , neuroscience , immunostaining , endocrinology , medicine , immunology , immunohistochemistry
The neuronal protein tyrosine phosphatases encoded by mouse gene Ptprr (PTPBR7, PTP‐SL, PTPPBSγ‐42 and PTPPBSγ‐37) have been implicated in mitogen‐activated protein (MAP) kinase deactivation on the basis of transfection experiments. To determine their physiological role in vivo , we generated mice that lack all PTPRR isoforms. Ptprr −/− mice were viable and fertile, and not different from wildtype littermates regarding general physiology or explorative behaviour. Highest PTPRR protein levels are in cerebellum Purkinje cells, but no overt effects of PTPRR deficiency on brain morphology, Purkinje cell number or dendritic branching were detected. However, MAP kinase phosphorylation levels were significantly altered in the PTPRR‐deficient cerebellum and cerebrum homogenates. Most notably, increased phospho‐ERK1/2 immunostaining density was observed in the basal portion and axon hillock of Ptprr −/− Purkinje cells. Concomitantly, Ptprr −/− mice displayed ataxia characterized by defects in fine motor coordination and balance skills. Collectively, these results establish the PTPRR proteins as physiological regulators of MAP kinase signalling cascades in neuronal tissue and demonstrate their involvement in cerebellum motor function.