Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in the gene for epsilon sarcoglycan (epsilon-SG) are associated with a disorder of the central nervous system, the myoclonus-dystonia syndrome (MDS; DYT11). In contrast, mutations of other sarcoglycan family members lead to limb-girdle muscular dystrophies. To establish the framework for functional studies of epsilon-SG, we cloned rat epsilon-SG cDNA, quantified epsilon-SG mRNA levels in neural and non-neural tissues at different developmental time points with relative quantitative multiplex real-time reverse transcriptase PCR (RT-PCR), and characterized the distribution of epsilon-SG mRNA in brain with in situ hybridization. Rat epsilon-SG cDNA contains an open reading frame (ORF) of 1311 bp that encodes a 437-amino acid (aa) protein with 95.9% and 98.2% identity to human and mouse epsilon-SG amino acid sequences, respectively. Using real-time RT-PCR, epsilon-SG was detected in both neural (cerebellar cortex, striatum, cerebral cortex, thalamus, hippocampus) and non-neural (muscle, liver, kidney, heart) tissues at each developmental time point tested [Embryonic Day 20 (E20), Postnatal Day 1 (P1), P7, P14, P36, 6 months, 1.5 years). Levels of epsilon-SG mRNA were highest at E20 in all tissues. The developmental regulation of epsilon-SG mRNA expression was most striking in muscle with E20 and early postnatal epsilon-SG mRNA levels over 10 times higher than those seen in adult rats. In adult rats, epsilon-SG mRNA levels were several-fold higher in brain, particularly cerebellar cortex, than in muscle. Radioactive in situ hybridization showed that epsilon-SG mRNA was widely distributed in rat brain. Robust hybridization signal was obtained from regions with dense neuronal packing such as the hippocampus, cerebellar molecular layer, and cerebral cortex. Our results suggest that epsilon-SG participates in the development of both neural and non-neural tissues and contributes to neuronal structure in the adult central nervous system.
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PMID:Cloning, developmental regulation and neural localization of rat epsilon-sarcoglycan. 1462 80

A GAG deletion in the gene (TOR1A) for torsinA is associated with childhood-onset generalized dystonia (DYT1). Environmental factors may contribute to development of the phenotype since mutations in TOR1A are clinically penetrant in less than 40% of cases. Median age of onset is 10 and appearance of dystonia after 28 is rare. As a step towards understanding the temporal window of DYT1 disease penetrance, we have examined torsinA transcript and protein expression in rats from the embryonic period through adulthood. With relative quantitative multiplex real-time RT-PCR, we detected torsinA transcript in both neural (cerebellar cortex, striatum, cerebral cortex, thalamus and hippocampus) and non-neural (liver, kidney and heart) tissues at each developmental time point tested (embryonic day 20 [E20], postnatal day 1 [P1], P7, P14, P36, 6 months, 1.5 years). Levels of torsinA transcript were highest at E20 or P1 in all tissues examined except for the cerebellum where transcript levels peaked at P14. Early postnatal levels of torsinA transcript were over three times higher than those seen in adult rats. With quantitative radioactive in situ hybridization, torsinA transcript was widely distributed in brain at all ages with levels peaking at P14 in both cerebellum and striatum. TorsinA-immunoreactivity (IR) was present in neurons throughout the brain. TorsinA-IR was detected in perikarya, dendrites and axons but not nuclei. At P14, prominent expression of torsinA was noted in both striatal cholinergic interneurons and cerebellar Purkinje cells. Our results suggest that torsinA may contribute to postnatal maturational events in the brain such as dendritic arborization and synaptogenesis. Furthermore, the time course of torsinA expression in discrete components of motor networks is compatible with the temporal window of clinical penetrance in DYT1 mutation carriers.
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PMID:Developmental expression of rat torsinA transcript and protein. 1528 94

The genetically dystonic rat (SD-dt:JFL) is an autosomal recessive model of generalized dystonia. Without cerebellectomy, the dt rat dies prior to Postnatal Day 40. The dt locus was mapped to a 4.2 Mb region on Chr 7q11 and candidate genes were screened with semi-quantitative RT-PCR. Then, Southern blotting and genomic DNA sequencing identified the 3'-long terminal repeat portion of an intracisternal A particle element inserted into Intron 1 of Atcay, the gene which encodes caytaxin. Northern and Western blotting and quantitative real-time RT-PCR defined the Atcay allele in dt rats (Atcay(dt)) as hypomorphic. To establish a framework for functional studies of caytaxin, the developmental expression of rat Atcay transcript was analyzed with Northern blotting, relative quantitative multiplex real-time RT-PCR (QRT-PCR) and in situ hybridization. With a multiple tissue Northern blot, three Atcay transcripts were identified in brain but none were present in heart, spleen, lung, liver, muscle, kidney or testis. With a multiple time-point Northern blot, the same three transcripts were present in cerebellum at Embryonic Day (E15), Postnatal Day 1 (P1), P7, P14, P36 and 8 months. During early development (E15 to P14), the relative proportion of the smallest transcript was increased. QRT-PCR was performed with total RNA from cerebral cortex, striatum, thalamus, hippocampus and cerebellum. Transcript levels peaked at P7 in hippocampus, increased linearly from P1 to P36 in cerebellum, and showed minimal developmental regulation in cerebral cortex. Radioactive in situ hybridization localized Atcay transcript to seemingly all neuronal populations in brain. In cerebellum, Atcay transcript was present in the molecular, Purkinje and granular layers; transcript density in the molecular layer peaked at P14. In the background of previous biochemical, behavioral and electrophysiological studies in the dt rat, our data are compatible with a vital role for caytaxin in the development and neurophysiology of cerebellar cortex.
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PMID:Caytaxin deficiency causes generalized dystonia in rats. 1624 57