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Dystonin Expression in the Developing Nervous System Predominates in the Neurons That Degenerate indystonia musculorumMutant Mice

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Abstract

Dystonia musculorum (dt) is an inherited neurodegenerative disorder in mice. Thedtgene product, dystonin, contains the bullous pemphigoid antigen 1 coding region at its C-terminus and an actin binding domain at its N-terminus. We demonstrate that dystonin expression throughout mouse development predominates in neurons of the cranial and spinal sensory ganglia. These structures are the most severely affected in dystonic mice which could explain their severe sensory ataxia. Since we show expression in sensory neurons with small and large axoplasmic volumes, but degeneration is restricted primarily to the latter type, we suggest that caliber and size of the axon is an important factor in the disease process. Dystonin is also expressed in the extrapyramidal motor system and in the cerebellum. Functional defects in these cell types could account for the dystonic symptoms ofdtmice not explained by simple sensory denervation. We also detect dystonin expression in motor neurons most of which are unaffected by the degenerative process indtmice.

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    2016, Methods in Enzymology
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    For the study of neuronal dystonin in primary cells, we recommend using sensory neurons derived from DRGs. This is due to the consistently high expression of the neuronal BPAG1 isoforms in sensory neurons (Bernier et al., 1995; Dowling, Yang, Wollmann, Reichardt, & Fuchs, 1997), as well as its major involvement in the dt disease. It also seems that BPAG1 loss-of-function in sensory neurons is not compensated for by other members of the spectraplakin family (Leung et al., 2001), which makes this cell type ideal for investigating the specific cellular roles of BPAG1 isoforms.

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    2013, International Review of Cell and Molecular Biology
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    Dystonin-a is expressed in the spinal cord and brain at various embryonic and postnatal time points, including embryonic (E9.5–E16.5), postnatal (P3 and P42) and adult stages. Dystonin-a expression is highest at sexual maturity (P42) (Bernier et al., 1995). The presence of dystonin-a as early as E9.5 is interesting since the dt phenotype is only overtly obvious at approximately 2 weeks postnatal development.

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