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Publication : P-Rex2 regulates Purkinje cell dendrite morphology and motor coordination.

First Author  Donald S Year  2008
Journal  Proc Natl Acad Sci U S A Volume  105
Issue  11 Pages  4483-8
PubMed ID  18334636 Mgi Jnum  J:133335
Mgi Id  MGI:3778304 Doi  10.1073/pnas.0712324105
Citation  Donald S, et al. (2008) P-Rex2 regulates Purkinje cell dendrite morphology and motor coordination. Proc Natl Acad Sci U S A 105(11):4483-8
abstractText  The small GTPase Rac controls cell morphology, gene expression, and reactive oxygen species formation. Manipulations of Rac activity levels in the cerebellum result in motor coordination defects, but activators of Rac in the cerebellum are unknown. P-Rex family guanine-nucleotide exchange factors activate Rac. We show here that, whereas P-Rex1 expression within the brain is widespread, P-Rex2 is specifically expressed in the Purkinje neurons of the cerebellum. We have generated P-Rex2(-/-) and P-Rex1(-/-)/P-Rex2(-/-) mice, analyzed their Purkinje cell morphology, and assessed their motor functions in behavior tests. The main dendrite is thinned in Purkinje cells of P-Rex2(-/-) pups and dendrite structure appears disordered in Purkinje cells of adult P-Rex2(-/-) and P-Rex1(-/-)/P-Rex2(-/-) mice. P-Rex2(-/-) mice show a mild motor coordination defect that progressively worsens with age and is more pronounced in females than in males. P-Rex1(-/-)/P-Rex2(-/-) mice are ataxic, with reduced basic motor activity and abnormal posture and gait, as well as impaired motor coordination even at a young age. We conclude that P-Rex1 and P-Rex2 are important regulators of Purkinje cell morphology and cerebellar function.
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