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Abnormal dysbindin expression in cerebellar mossy fiber synapses in the mdx mouse model of Duchenne muscular dystrophy

Sillitoe, Roy V., Benson, Matthew A., Blake, Derek J. and Hawkes, Richard 2003. Abnormal dysbindin expression in cerebellar mossy fiber synapses in the mdx mouse model of Duchenne muscular dystrophy. Journal of Neuroscience 23 (16) , pp. 6576-6585.

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The dystrophin-associated protein complex (DPC), comprising sarcoglycans, dystroglycans, dystrobrevins, and syntrophins, is a component of synapses both in muscle and brain. Dysbindin is a novel component of the DPC, which binds to β-dystrobrevin and may serve as an adaptor protein that links the DPC to an intracellular signaling cascade. Disruption of the DPC results in muscular dystrophy, and mutations in the human ortholog of dysbindin have been implicated in the pathogenesis of schizophrenia. In both cases, patients also present with neurological symptoms reminiscent of cerebellar problems. In the mouse cerebellum, dysbindin immunoreactivity is expressed at high levels in a subset of mossy fiber synaptic glomeruli in the granular layer. Lower levels of dysbindin immunoreactivity are also detected in Purkinje cell dendrites. In the cerebellar vermis, dysbindin-immunoreactive glomeruli are restricted to an array of parasagittal stripes that bears a consistent relationship to Purkinje cell parasagittal band boundaries as defined by the expression of the respiratory isoenzyme zebrin II/aldolase c. In a mouse model of Duchenne muscular dystrophy, the mdx mutant, in which dystrophin is not expressed, there is a dramatic increase in the number of dysbindin-immunoreactive glomeruli in the posterior cerebellar vermis. Moreover, the topography of the terminal fields is disrupted, replacing the stripes by a homogeneous distribution. Abnormal synaptic organization in the cerebellum may contribute to the neurological problems associated with muscular dystrophy and schizophrenia.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Purkinje cell, dystrophin, zebrin II, unipolar brush cell, choline acetyltransferase, schizophrenia
Additional Information: Pdf uploaded in accordance with publisher's policy at (accessed 27/02/2014).
Publisher: Society for Neuroscience
ISSN: 0270-6474
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 05:10

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