Exclusive paternal expression and novel alternatively spliced variants of ε‐sarcoglycan mRNA in mouse brain

Yokoi, Fumiaki; Dang, Mai T.; Mitsui, Shinichi; Li, Yu Qing

doi:10.1016/j.febslet.2005.07.065

Cited by 29 publications

(47 citation statements)

References 36 publications

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“…In this study, we show that the SGCE imprinting pattern is retained in different human brain regions and different human tissues (muscle, blood) similar to what has been shown in mice. 18 Thus, the brain-specific M-D phenotype cannot be explained by a brain region-or tissue-specific imprinting. As not all M-D patients have mutations in SGCE, silencing of SGCE expression owing to imprinting defects could also be a possible disease mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…Monoallelic paternal SGCE expression has been shown in human blood leukocytes and in human and mice brain. 15,18 Several genes are known to show tissue-specific imprinting 22 and brain cell-type-or region-specific imprinting. 23 The latter has not yet been investigated for SGCE, but is important to address, as only regions in which the imprint is maintained can be involved in the M-D pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…17 Recently, a new brain-specific alternatively spliced exon (exon 11c, an elongated exon 11b) has been identified in mice. 18 Transcripts containing either exon 11b or 11c encode proteins with a different C-terminal sequence containing a PDZ-binding motif. This motif is a protein-interaction domain and thus may contribute to a unique SGCE function in the brain.…”

Section: Myoclonus-dystonia (M-d) Is a Movement Disorder Characterizedmentioning

confidence: 99%

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SGCE isoform characterization and expression in human brain: implications for myoclonus–dystonia pathogenesis?

et al. 2010

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Myoclonus-dystonia (M-D) is a neurological movement disorder with involuntary jerky and dystonic movements as major symptoms. About 50% of M-D patients have a mutation in e-sarcoglycan (SGCE), a maternally imprinted gene that is widely expressed. As little is known about SGCE function, one can only speculate about the pathomechanisms of the exclusively neurological phenotype in M-D. We characterized different SGCE isoforms in the human brain using ultra-deep sequencing. We show that a major brain-specific isoform is differentially expressed in the human brain with a notably high expression in the cerebellum, namely in the Purkinje cells and neurons of the dentate nucleus. Its expression was low in the globus pallidus and moderate to low in caudate nucleus, putamen and substantia nigra. Electrophysiological studies in man suggest that myoclonic symptoms are of subcortical origin. [1][2][3] In general, dystonia is thought to arise from dysfunction of the basal ganglia. 4 About 50% of M-D patients who were classified as definite M-D carry a mutation in the widely expressed e-sarcoglycan (SGCE). [5][6][7] The genetic cause in the remaining patients is still unclear. A second locus has been reported in one large M-D family (DYT15, 18p11), but no gene has been identified yet. 8,9 SGCE is part of the sarcoglycan family that consists of N-glycosylated transmembrane proteins. Six different sarcoglycans have been identified so far (a-, b-, g-, d-, e-and z-), but little is known about the function of particular sarcoglycan members and their function in different tissues. 10 In muscles, sarcoglycans form a heterotetrameric complex that is constituent of the dystrophinassociated protein complex. This complex mediates the structural stability of the plasma membrane and interactions between the extracellular matrix and the cytoskeleton. 11 Mutations in other sarcoglycans, a-, b-, g-and d-sarcoglycan, lead to different forms of limb-girdle muscular dystrophy, characterized by progressive muscle weakness. 10 Little is known about composition and function of the dystrophin-associated protein complex in the brain. SGCE is highly homologous to a-sarcoglycan, 12 but no muscle

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Myoclonus-dystonia (M-d) Is a Movement Disorder Characterizedmentioning

confidence: 99%

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SGCE isoform characterization and expression in human brain: implications for myoclonus–dystonia pathogenesis?

et al. 2010

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“…The protein sequence homology analysis and 3D structure modeling suggest that "-sarcoglycans has a cadherin-like domain at the N-terminal extracellular region, suggesting it may function in intercellular adhesion (26). Mouse "-sarcoglycan has alternative splicing variants and the brain-specific isoforms have PDZ-binding motifs (27). Mouse "-sarcoglycan is enriched in pre-and post-synaptic membrane fractions, suggesting a role in synaptic transmission (28).…”

mentioning

confidence: 99%

“…Mouse "-sarcoglycan is enriched in pre-and post-synaptic membrane fractions, suggesting a role in synaptic transmission (28). Sgce is maternally imprinted and paternally expressed in humans and rodents (27,29,30). We previously reported the making of Sgce KO mice lacking exon 4 and demonstrated that paternally inherited Sgce heterozygous KO mice did not express maternally inherited WT Sgce in the brain (27).…”

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Earlier onset of motor deficits in mice with double mutations in Dyt1 and Sgce

Yokoi

Yang

et al. 2010

The Journal of Biochemistry

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Deleterious Effects of Beta-Blockers on Survival in Patients With Cirrhosis and Refractory Ascites†,‡

Mélot²,

et al. 2010

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Beta-blockers may have a negative impact on survival in patients with cirrhosis and refractory ascites. The aim of this study was to evaluate the effect of the administration of betablockers on long-term survival in patients with cirrhosis and refractory ascites. We performed a single-center, observational, case-only, prospective study of patients with cirrhosis and refractory ascites who did or did not receive beta-blockers for the prevention of gastrointestinal bleeding; 151 patients were included. The mean Model for End-Stage Liver Disease score was 18.8 6 4.1. All patients regularly underwent large-volume paracentesis and intravenous albumin administration. Seventy-seven patients (51%) were treated with propranolol (113 6 46 mg/day). The median follow-up for the whole group was 8 months. The median survival time was 10 months [95% confidence interval (CI) 5 8-12 months]. The probability of survival at 1 year was 41% (95% CI 5 33%-49%). The clinical characteristics and laboratory values at enrolment were not significantly different between patients who were receiving propranolol and those who were not. The median survival time was 20.0 months (95% CI 5 4.8-35.2 months) in patients not treated with propranolol and 5.0 months (95% CI 5 3.5-6.5 months) in those treated with propranolol (P 5 0.0001). The 1-year probability of survival was significantly lower in patients who received propranolol [19% (95% CI 5 9%-29%)] versus those who did not [64% (95% CI 5 52%-76%), P < 0.0001]. The independent variables of mortality were Child-Pugh class C, hyponatremia and renal failure as causes of refractory ascites, and beta-blocker therapy. Conclusion: The use of beta-blockers is associated with poor survival in patients with refractory ascites. These results suggest that betablockers should be contraindicated in these patients.

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Exclusive paternal expression and novel alternatively spliced variants of ε‐sarcoglycan mRNA in mouse brain

Cited by 29 publications

References 36 publications

SGCE isoform characterization and expression in human brain: implications for myoclonus–dystonia pathogenesis?

SGCE isoform characterization and expression in human brain: implications for myoclonus–dystonia pathogenesis?

Earlier onset of motor deficits in mice with double mutations in Dyt1 and Sgce

Deleterious Effects of Beta-Blockers on Survival in Patients With Cirrhosis and Refractory Ascites†,‡

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