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)

We present yotari, a novel neurological mutant mouse whose mutation is transmitted in an autosomal recessive manner. The phenotype of yotari is very similar to that of reeler. yotari mutants are recognizable by their unstable gait and tremor and by their early deaths at around the time of weaning. The cerebella of homozygous yotari are hypoplastic and have no foliation. A molecular and a granular cell layer can be identified, but Purkinje cells are scattered throughout both the granular layer and white matter. The laminar structure of the cerebral cortex and the hippocampal formation are also distorted. To test whether the mutated gene in yotari is the reeler gene, reelin, yotari heterozygotes were mated with reeler homozygotes or heterozygotes. The absence of abnormal offspring indicated that the yotari gene is distinct from reelin. Furthermore, expression of mRNA and protein of reelin was verified by Northern blotting and immunohistochemistry using a CR-50 monoclonal antibody (mAb) which is specific to Reelin, the reelin gene product. Although the mutation of several genes, including cyclin-dependent kinase 5 (Cdk 5), p35 and LIS1, 45 kDa subunits of platelet-activating factor acetylhydrolase (PAF-AH) Ib, in Miller-Dieker lissencephaly syndrome (MDS) has been reported to cause abnormal laminar structure in the brain, no abnormality was found in yotari by Western blotting with antibodies (Ab's) against these molecules. The close similarity of the phenotypes of yotari and reeler and the expression of reelin in yotari may suggest that the gene mutated in yotari encodes a molecule that is on the same signaling pathway as Reelin, the product of reelin. yotari will provide valuable clues to explore the molecular mechanism of neuronal migration and orderly laminar structure formation of the brain.
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PMID:A novel neurological mutant mouse, yotari, which exhibits reeler-like phenotype but expresses CR-50 antigen/reelin. 943 47

Reeler, an autosomal recessive mutant mouse, is characterized by ataxic gait and tremor. In this mutant, the cerebral and cerebellar cortices and hippocampus are cytoarchitectually disorganized: neuronal components are ectopically located in these laminated structures. Since reelin, the gene responsible for the reeler mutation, was discovered by D'Arcangelo et al. (Nature 374: 719-723, 1995), remarkable progress has occurred in this field. The reelin gene encodes an extracellular protein, Reelin, that is crucial for neuronal migration. During embryogenesis, reelin is expressed in the Cajal-Retzius cells in the cerebral cortex and in the outer granule cells in the cerebellar cortex. Although non-laminated structures such as facial nucleus, inferior olivary complex, and dorsal cochlear nucleus are also cytoarchitectually deranged in this mutant, only a few studies have been done to clarify the detailed abnormalities in these non-laminated structures. In this review, we focused on the cytoarchitectonic abnormality in the facial nucleus of the reeler mouse. The branchiomotor neurons in the facial nucleus are generated from the ventricular zone of the floor of the fourth ventricle, migrate ventrolaterally, and finally settle near the ventral surface of the hindbrain. Time schedules for the generation, axon formation and migration of facial motoneurons are similar both in the normal and reeler mice, but the reeler phenotype becomes identifiable at the end of neuronal migration. Although the reason why the facial nucleus is cytoarchitectually abnormal in the reeler mouse is still unknown, the long migration of the facial motoneurons seems to be susceptible to the absence of Reelin in the reeler mouse. In spite of the cytoarchitectual abnormality, retrograde horseradish peroxidase (HRP) study confirmed that the musculotopic arrangements within the facial nucleus of the reeler mouse are still preserved, suggesting that neuronal migration and target recognition are regulated independently. More recently, other reeler-like mutants have been reported. Among them, yotari and scrambler mice arise from mutations in mdab1, a mouse gene related to Drosophila gene disabled (dab). More than 10 years ago, an autosomal recessive rat mutant, shaking rat Kawasaki (SRK), was described that exhibits a phenotype identical to reeler, but the gene responsible for this rat mutation remains unknown. Interestingly, the facial nucleus is cytoarchitectually more deranged in yotari and SRK than their reeler counterpart. Although the reason why yotari exhibits a phenotype identical to reeler in the laminated structures but not in non-laminated structures such as the facial nucleus has remained obscure, mDab1 and Reelin proteins may function as signaling molecules in a different way between laminated and non-laminated structures. Phenotypes resembling that of reeler are seen with mutations in mdab1, cdk5 and p35. Cdk5 and p35 are respectively the catalytic and regulatory subunits of a serine/threonine kinase, that could potentially operate in a common signalling pathway with mDab and Reelin. These plausible partners for Reelin and mDab1 should help us to understand how the activities of these proteins coordinate neuronal migration and rearrangement.
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PMID:[Cytoarchitectonic abnormality in the facial nucleus of the reeler mouse]. 1049 86

Shaking Rat Kawasaki (SRK) is a Reelin-deficient rat, that shows significant cytoarchitectural abnormalities in the cerebral and cerebellar cortices in a similar manner to the reeler malformation. In the present study, we investigated the cytoarchitecture and myeloarchitecture of the superior colliculus (SC) of this mutant rat. The Nissl staining clearly showed that neuronal components in the superficial layers of the SC in SRK rat were intermingled with each other and that the boundaries between these superficial layers were blurred. The MBP immunohistochemistry showed an abnormal fiber pattern in the superficial layers of the SC of this mutant rat. In the normal rat, myelinated fibers passed rostrocaudally through the optic layer, and only a few myelinated fibers were recognized in the uppermost two layers, i.e., the zonal and superficial gray layers. By contrast, in SRK rat, the myelinated fibers were distributed throughout the entire thickness of the superficial layers of the SC. Anterograde labeling of retinotectal fibers with an injection of Cholera Toxin subunit B into the retina revealed that this abnormal fiber pattern was associated with the anomalous course of the retinotectal fibers. No distinct differences in the cytoarchitecture and fiber pattern in the deep layers of the SC were seen. In conclusion, the present study demonstrated that the cytoarchitecture and fiber patterning in the superficial layers of the SC were disrupted in SRK rat, suggesting that Reelin protein regulates the formation of the superficial layers of the SC.
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PMID:Cytoarchitecture and fiber pattern of the superior colliculus are disrupted in the Shaking Rat Kawasaki. 1264 43

The shaking rat Kawasaki (SRK) is an autosomal recessive mutant that exhibits reeler-like abnormal locomotor behaviors. The murine reeler mutants arise from several mutations in the specific gene called reelin, which result in defects of Reelin expression or secretion in the cerebral cortex and other regions of CNS. To address the issue of whether the SRK mutation also arises from a mutation in reelin, we analyzed the reelin gene in SRK. Northern analysis of reelin mRNA from normal rats showed that rat reelin was expressed as a approximately 12-kb transcript in both the cerebrum and the cerebellum, whereas reelin expression was markedly reduced in the SRK brains. In situ hybridization analysis showed that reelin mRNA in the SRK brains was expressed in Cajal-Retzius cells in the marginal zone of the cerebral cortex and outer granular cells in the cerebellar cortex in similar manners to normal controls, but its expression was considerably reduced. On Western blotting and immunohistochemical analyses using antibodies specific for the Reelin protein, no immunoproduct was recognized in the cerebral and cerebellar cortices. From the cDNA sequences, we found a 64-base heterologous sequence in SRK reelin, which contains a termination codon in the reading frame. Furthermore, genomic DNA analysis revealed that a 10-base deletion, which contains a predicted splice donor site, occurred in the SRK genomic reelin gene, resulting in "read through" into the following intron in SRK. Thus, the SRK mutation is another type of mutation that lacks expression of the functional Reelin protein and, therefore, causes the reeler phenotype.
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PMID:Missplicing resulting from a short deletion in the reelin gene causes reeler-like neuronal disorders in the mutant shaking rat Kawasaki. 1282 Jan 63

Reelin is a neuronal glycoprotein that plays a crucial role in brain layer formation during prenatal development. The reeler mutant mouse lacks Reelin, leading to abnormalities in the neuronal layering of cerebral cortex and cerebellum, producing ataxia, tremor and abnormal locomotion. Reeler mice are reported to have growth retardation and most of them are sterile or unable to bring up their newborns. Since the brain is one of the main regulator of pituitary hormone secretion and no information was reported regarding pituitary function and structure in these mutant mice, we studied pituitary endocrine activity and morphology in reeler mice. Mice were classified in three groups as reeler homozygote (RHM), reeler heterozygote (RHT) or control (CO). Pituitary hormone blood levels were assessed by enzyme immunoassay (EIA) and immunoradiometric assay (IRMA). Animals and their pituitaries were weighted and pituitaries were studied by histology, immunohistochemistry and electron microscopy. Results showed statistically significant differences in body weight and in adrenocorticotropic hormone (ACTH) and luteinizing hormone (LH) blood levels between the three groups. In contrast, growth hormone (GH) blood levels showed a high individual variation and no decrease in reeler groups compared with CO. Morphological studies revealed no differences in pituitary cell types except that somatotrophs appeared to be slightly smaller in RHM and RHT. Although it seems that pituitary hypofunction is not responsible for growth retardation, more studies are needed to obtain a deeper insight into the endocrine status of these mutant mice to elucidate the cause of their low body weight and reproductive behaviour.
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PMID:Hormonal and morphological study of the pituitaries in reeler mice. 1750 46

The rat granular retrosplenial cortex (GRS) is a simplified cortex, with distinct stratification and, in the uppermost layers, distinct modularity. Thalamic and cortical inputs are segregated by layers and in layer 1 colocalize, respectively, with apical dendritic bundles originating from neurons in layers 2 or 5. To further investigate this organization, we turned to reelin-deficient reeler mouse and Shaking rat Kawasaki. We found that the disrupted lamination, evident in Nissl stains in these rodents, is in fact a patch-matrix mosaic of segregated afferents and dendrites. Patches consist of thalamocortical connections, visualized by vesicular glutamate transporter 2 (VGluT2) or AChE. The surrounding matrix consists of corticocortical terminations, visualized by VGluT1 or zinc. Dendrites concentrate in the matrix or patches, depending on whether they are OCAM positive (matrix) or negative (patches). In wild-type rodents and, presumably, mutants, OCAM(+) structures originate from layer 5 neurons. By double labeling for dendrites (filled by Lucifer yellow in fixed slice) and OCAM immunofluorescence, we ascertained 2 populations in reeler: dendritic branches either preferred (putative layer 5 neurons) or avoided (putative supragranular neurons) the OCAM(+) matrix. We conclude that input-target relationships are largely preserved in the mutant GRS and that dendrite-dendrite interactions involving OCAM influence the formation of the mosaic configuration.
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PMID:Unusual patch-matrix organization in the retrosplenial cortex of the reeler mouse and Shaking rat Kawasaki. 1772 62