Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A group of inherited neurological disorders are the X-chromosome linked dysmyelinoses, in which myelin membranes of the CNS are missing or perturbed due to a strongly reduced number of differentiated oligodendrocytes. In animal dysmyelinoses (jimpy mouse, msd-mouse, md rat, shaking pup) mutations of the main integral myelin membrane protein, proteolipid protein, have been identified. Pelizaeus-Merzbacher disease (PMD) or sudanophilic leucodystrophy is an X-linked dysmyelinosis in humans. We report here on the molecular basis of the defect of affected males of a PMD kindred. Rearrangements of the PLP gene were excluded by Southern blot hybridisation analysis and PCR amplification of overlapping domains of the PLP gene. Sequence analysis revealed one single C----T transition in exon IV, which leads to a threonine----isoleucine substitution within a hydrophobic intramembrane domain. The impact of this amino-acid exchange on the structure of PLP in the affected cis membrane domain is discussed. A space filling model of this domain suggests a tight packing of the alpha-helices of the loop which is perturbed by the amino-acid substitution in this PMD exon IV mutant. The C----T transition in exon IV abolishes a Hph I restriction site. This mutation at the recognition site for Hph I (RFLP) and allele-specific primers have been used for mutation screening the PMD kindred.
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PMID:A point mutation at the X-chromosomal proteolipid protein locus in Pelizaeus-Merzbacher disease leads to disruption of myelinogenesis. 170 72

Paralytic tremor (pt) is a sex-linked mutation in rabbit that affects myelination of the CNS. Myelin in the pt brains represents approximately 30% of the normal levels. Previously we showed that the pt mutation affects primarily proteolipid protein (Plp) gene expression. In the present study we investigated the relative effect of the pt mutation on two distinctive Plp gene products, PLP- and DM-20-specific messenger RNAs. Our results showed that both PLP and DM-20 are affected and that the ratio DM-20/PLP was higher in pt rabbits than in age-matched controls. We sequenced normal rabbit PLP cDNA and characterized pt mutation at the DNA level. Rabbit PLP sequence, deduced from cDNA, differs from the human protein only at Thr198. Sequence analysis of the mutant cDNA revealed a transversion T-->A in exon 2 of the Plp gene. This point mutation, which is placed at the end of the first potential transmembrane domain, results in a substitution of His36 by a glutamine. This transversion abolishes a restriction site that enabled us to screen a large number of animals and observe a perfect correlation between the pt allele and the abnormal phenotype.
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PMID:Paralytic tremor (pt): a new allele of the proteolipid protein gene in rabbits. 752 75

The paralytic tremor (pt) rabbit is an X-linked recessive mutant characterized by hypomyelination of the CNS. The onset of myelin mutants' neurological symptoms typically occurs about the tenth postnatal day. A partial recovery is often observed; thus, the life-span of affected animals is almost normal and they can breed successfully. Mutants presenting this phenotype were chosen for our study. Because proteins can serve as excellent markers for the myelin formation process, we examined the developmental expression of several important myelin proteins (PLP/DM-20, MBP, CNP, MAG, and MOG) in both pt mutant and control rabbit brain homogenates. Expression of the investigated proteins occurs in rabbits as follows: CNP and MAG are already present at the early postnatal stage; PLP/DM-20 and MBP appear about the 10th postnatal day; MOG, expressed last, has been detected on the 28th postnatal day. Whereas the MBP, CNP, MAG, and MOG content is only slightly reduced in mature pt mutant brain homogenates (80-90% of control values), the amount of PLP corresponds to approximately 30-40% of that present in controls. Expression of all of the examined proteins is substantially retarded in maturing brains, which leads to the conclusion that besides severe PLP deficiency, retardation of oligodendrocyte maturation is another probable feature of pt mutation.
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PMID:Expression of myelin-specific proteins during development of normal and hypomyelinated Paralytic tremor mutant rabbits. I. Studies on the brain homogenates. 858 24

An X-linked, recessive paralytic tremor (pt) mutation is characterized by CNS hypomyelination. In our previous work, we presented developmental studies on the expression of several myelin-specific proteins (PLP/DM-20, MBP, CNP, MAG, and MOG) in the brain homogeates of both pt mutant and age-matched control Chinchilla rabbits aged 1-120 postnatal days. A moderate reduction in all examined proteins and a striking PLP deficiency were observed in the pt mutant rabbits. In the present study, we investigated isolated and purified myelin fractions. A severe (approximately 30% of control values) and approximately constant hypomyelination of pt mutant CNS was observed during the entire investigated development (28-120 postnatal days). Although the neurological symptoms gradually regressed and a partial recovery of the affected animals usually occurred, no tendency toward regression of the hypomyelination was noticed. Whereas the content of CNP, MBP, and MAG in isolated myelin membrane fractions seemed close to normal, a drastic PLP deficiency was observed. A significantly elevated amount of MOG was found in the myelin of pt mutant rabbits. The controversy between the high degree of hypomyelination and the slight reduction in myelin protein marker expression (except for PLP) in mature brain homogenates is discussed with respect to retarded oligodendrocyte maturation and deficient processing of myelin membranes in pt mutant rabbits.
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PMID:Expression of myelin-specific proteins during development of normal and hypomyelinated Paralytic tremor mutant rabbits. II. Studies on the purified myelin. 858 25

Paralytic tremor (Plp-pt) is a missense mutation of the myelin proteolipid gene (Plp) in rabbits. The myelin yield in the Plp-pt brain is reduced and the protein and lipid composition of central nervous system (CNS) myelin is abnormal. We studied the intracellular transport of the normal and Plp-pt mutant PLP and DM-20 in transiently transfected Cos-7 cells. While the mutant PLP accumulates in the rough endoplasmic reticulum and does not reach the plasma membrane, the spliced isoform of PLP, mutant DM-20, is normally transported to the cell surface and integrated into the membrane. Analysis of rabbit sciatic nerves revealed that concentration of peripheral nervous system (PNS) myelin proteins is normal in Plp-pt myelin. In the PNS like in the CNS, the level of Plp gene products is subnormal. But this does not affect myelination in the PNS where PLP, present in low concentration, is not a structural component of compact myelin. The normal level of Plp gene expression in Schwann cells is low and these results suggest that, in the Plp-pt PNS, Schwann cell function is not affected by the deficiency in PLP and/or the impairment of intracellular PLP transport.
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PMID:Proteolipid/DM-20 proteins bearing the paralytic tremor mutation in peripheral nerves and transfected Cos-7 cells. 873 35

Myelin/oligodendrocyte glycoprotein (MOG) is a minor myelin protein that belongs to the immunoglobulin gene superfamily and evokes demyelination based on immunological response. Localized preferentially at the external surfaces of myelin sheaths, it is one of the primarily target autoantigens in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Elevated MOG content has been found in the myelin fraction of the rabbits affected by the mild form of paralytic tremor (pt) disease, evoked by natural, point mutation in exon 2 of plp gene. A single T-->A transversion results in substitution of histidine36 by glutamine in PLP and it's splicing variant DM-20 molecules. The affected animals, although strictly controlled for pt trait, differ significantly in their phenotypes, distinguished by the severity of neurological symptoms. It was shown that the degree of CNS hypomyelination and deficiency of PLP/DM-20 correlates well with the severity of neurological symptoms and is highest in the most strongly affected animals. Variety of phenotypes generated from pt genotype together with previously observed MOG hyperexpression suggested possible contribution of immunological component to the pt disease. Present studies indicate that MOG expression depends both on the phenotype and the age of affected rabbits and most probably mirrors retardation in myelinogenesis process caused by pt mutation.
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PMID:pt point mutation in plp gene results in hyperexpression of MOG in hypomyelinated rabbit. 878 15

This study describes a new sex-linked myelin mutation in the mouse, jimpy 4J (Plpjp-4J), located in or very close to the proteolipid protein (Plp) gene. The Plpjp-4J/Y phenotype includes tremor, seizures, death during the 4th postnatal week, and the most severe central nervous system hypomyelination yet described in any mouse carrying a single myelin mutation. The few myelin sheaths are present in early myelinating areas where they form clusters of thin, usually loosely wrapped membranes which show several variations of morphology at their extracellular leaflets. Numbers of mature oligodendrocytes are sharply reduced; pycnotic glial nuclei and foamy cells are numerous. Astrocytosis is a prominent feature. No PLP protein is detected by immunoblotting in Plpjp-4J/Y brain but in spinal cord a faint band is present. Myelin basic protein and characteristic myelin lipids are also sharply reduced in both brain and spinal cord. Despite the qualitative similarity of the phenotypes reported in these and previous studies, DNA analysis demonstrate that Plpjp-4J is not a recurrence of the well known Plp mouse mutations jimpy (Plpjp) or myelin synthesis deficiency (Plpjp-msd).
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PMID:Jimpy 4J: a new X-linked mouse mutation producing severe CNS hypomyelination. 882 19

A 37-year-old woman was admitted to the hospital on October 4, 1991 because of fever, headache, and abnormal behavior. Although she was treated with aciclovir, she developed encephalitis, which slowly manifested itself over the next month as meningeal irritation, loss of consciousness, partial seizure, and quadriparesis. Her cerebrospinal fluid showed mild lymphocytic pleocytosis without protein elevation. Serum IgG antibody titer to rubella virus was elevated, but the rubella virus could not be detected in the cerebrospinal fluid by PCR amplification. Her consciousness level improved slowly, and by the end of November she suffered only dystonic posture of her right arm and hand. By the middle of December, there were no abnormal neurological findings except some extrapyramidal tract signs and symptoms, such as tremor and rigidity. The serum rubella virus IgG titer had fallen back into the normal range. Her illness was diagnosed as subacute panencephalitis, and she recovered completely about 5 months after the onset of the disease. The lack of rubella virus in the cerebrospinal fluid suggests that panencephalitis may not be dependent on virus replication within the central nervous system. Specific T cells sensitized to proteolipid protein synthetic peptides (PLP158-166) identified with rubella virus were detected in this case during the active stage. These observations imply that subacute panencephalitis may be dependent on an immune-mediated mechanism and that PLP-specific T cells may play an important role in pathogenesis of the disease.
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PMID:[A case report of subacute panencephalitis associated with specific T cells sensitized to proteolipid protein (PLP) synthetic peptides identified with rubella virus]. 897 31

During the sixties a sex-specific, hereditary form of congenital tremor type A (CT A) appeared which was classified as CT AIII. The symptoms were the same as in other subtypes and only autopsy and differential diagnosis showed the distinctive signs of this disease. Pigs suffering from CT AIII fail to develop a tight myelin sheath and contain a reduced number of oligodendrocytes in their CNS whereas no pathological changes can be detected in the PNS. The same symptoms as with CT AIII appear in various disorders in animals and humans. The cause for jimpy in mice was traced back to a mutation in the PLP gene. In the course of these findings different mutations in the human PLP gene were identified and shown to be the reason for the rare Pelizaeus-Merzbacher-Disease and the spastic paraplegia type 2. If one considers the clinical and histological similarities between PLP mutants and CT AIII in pigs it is reasonable to assume that this X-linked gene plays a major role in the development of CT AIII. In the following we describe the isolation and characterization of the porcine PLP gene and its possible involvement in congenital tremor type AIII.
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PMID:[The role of proteolipid proteins in the development of congenital tremors type AIII: a review]. 903 71

We previously showed that the jimpy-4J mouse mutation is located on the X chromosome, in or closely linked to the proteolipid protein (Plp) gene. The phenotype is characterized by the most severe hypomyelination of any of the naturally occurring myelin mutant mice, sharp reduction in oligodendrocyte number, and virtual absence of PLP protein. Affected animals show tremor, seizures, and die at about 24 postnatal days. We now report that sequencing of Plp genomic and cDNAs identifies a single nucleotide substitution in exon 2 that predicts an Ala38Ser substitutions in a hydrophilic region of PLP/DM20 protein close to a transmembrane domain. This mutation occurs in a very different region of the mouse Plp gene than that jimpy-msd mutations, yet all three produce qualitatively similar phenotypes.
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PMID:Jimpy-4J mouse has a missense mutation in exon 2 of the Plp gene. 921 79


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