Regions downstream from the WW domain of dystrophin are important for binding to postsynaptic densities in the brain

Sakamoto, Tetsuro; Arima, Toshiyuki; Ishizaki, Masatoshi; Kawano, Ryoko; Koide, Tatsuya; Uchida, Yuji; Yamashita, Satoshi; Hirano, Teruyuki; Maeda, Yasushi; Uchino, Makoto

doi:10.1016/j.nmd.2008.02.004

Cited by 6 publications

(1 citation statement)

References 41 publications

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“…DMD muscles lack the dystrophin protein, and dystrophin gene replacement is expected to halt ongoing myofiber turnover. To drive the transcription of various genes in gene therapy protocols, several strong viral enhancer/promoters were used in previous studies, including cytomegalovirus (CMV) [11], [12],[13], Raus sarcoma virus (RSV) [14], [15], [16], cytomegalovirus enhancer, chicken beta-actin (CAG) promoter [16], [17], [18], [19], murine stem cell virus (MSCV) [16], [17], [20], [21], mouse phosphoglycerate-kinase 1 (pGK) [12], [22], [23], and elongation factor 1 (EF1) [12], [24], which are ubiquitous promoters derived from house keeping gene regulation systems in mammalian cells. As the MSCV promoter drives gene expression as strongly as the CMV promoter and achieves stable gene expression in different type of cells, especially muscle fibers, we previously used the MSCV promoter to regulate the expression of a short version of the dystrophin gene in a lentiviral vector [6].…”

Section: Introductionmentioning

confidence: 99%

Muscle Fiber Type-Predominant Promoter Activity in Lentiviral-Mediated Transgenic Mouse

et al. 2011

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Variations in gene promoter/enhancer activity in different muscle fiber types after gene transduction was noticed previously, but poorly analyzed. The murine stem cell virus (MSCV) promoter drives strong, stable gene expression in hematopoietic stem cells and several other cells, including cerebellar Purkinje cells, but it has not been studied in muscle. We injected a lentiviral vector carrying an MSCV-EGFP cassette (LvMSCV-EGFP) into tibialis anterior muscles and observed strong EGFP expression in muscle fibers, primary cultured myoblasts, and myotubes isolated from injected muscles. We also generated lentiviral-mediated transgenic mice carrying the MSCV-EGFP cassette and detected transgene expression in striated muscles. LvMSCV-EGFP transgenic mice showed fiber type-dependent variations in expression: highest in types I and IIA, intermediate in type IID/X, and lowest in type IIB fibers. The soleus and diaphragm muscles, consisting mainly of types I and IIA, are most severely affected in the mdx mouse model of muscular dystrophy. Further analysis of this promoter may have the potential to achieve certain gene expression in severely affected muscles of mdx mice. The Lv-mediated transgenic mouse may prove a useful tool for assessing the enhancer/promoter activities of a variety of different regulatory cassettes.

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Section: Introductionmentioning

confidence: 99%

Muscle Fiber Type-Predominant Promoter Activity in Lentiviral-Mediated Transgenic Mouse

et al. 2011

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Quantitative changes of nicotinic receptors in the hippocampus of dystrophin-deficient mice

et al. 2012

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Lack of dystrophin in Duchenne muscle dystrophy (DMD) and in the mutant mdx mouse results in progressive muscle degeneration, structural changes at the neuromuscular junction, and destabilization of the nicotinic acetylcholine receptors (nAChRs). One-third of DMD patients also present non-progressive cognitive impairments. Considering the role of the cholinergic system in cognitive functions, the number of nAChR binding sites and the mRNA levels of α4, β2, and α7 subunits were determined in brain regions normally enriched in dystrophin (cortex, hippocampus and cerebellum) of mdx mice using specific ligands and reverse-transcription polymerase chain reaction assays, respectively. Membrane preparations of these brain regions were obtained from male control and mdx mice at 4 and 12 months of age. The number of [³H]-cytisine (α4β2) and [¹²⁵I]-α-bungarotoxin ([¹²⁵I]-αBGT, α7) binding sites in the cortex and cerebellum was not altered with age or among age-matched control and mdx mice. A significant reduction in [³H]-cytisine (48%) and [¹²⁵I]-αBGT (37%) binding sites was detected in the hippocampus of mdx mice at 12 months of age. When compared with the age-matched control groups, the mdx mice did not have significantly altered [³H]-cytisine binding in the hippocampus, but [¹²⁵I]-αBGT binding in the same brain region was 52% higher at 4 months and 20% lower at 12 months. mRNA transcripts for the nAChR α4, β2, and α7 subunits were not significantly altered in the same brain regions of all animal groups. These results suggest a potential alteration of the nicotinic cholinergic function in the hippocampus of dystrophin-deficient mice, which might contribute to the impairments in cognitive functions, such as learning and memory, that have been reported in the dystrophic murine model and DMD patients.

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Interleukin-6: A neuro-active cytokine contributing to cognitive impairment in Duchenne muscular dystrophy?

Stephenson

Rae

2020

Cytokine

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Regions downstream from the WW domain of dystrophin are important for binding to postsynaptic densities in the brain

Cited by 6 publications

References 41 publications

Muscle Fiber Type-Predominant Promoter Activity in Lentiviral-Mediated Transgenic Mouse

Muscle Fiber Type-Predominant Promoter Activity in Lentiviral-Mediated Transgenic Mouse

Quantitative changes of nicotinic receptors in the hippocampus of dystrophin-deficient mice

Interleukin-6: A neuro-active cytokine contributing to cognitive impairment in Duchenne muscular dystrophy?

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