| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Reeler mouse is an autosomal recessive mutant mouse, and characterized by ataxic gait and tremor. Since reelin, the gene responsible for the reeler mutation is discovered by D'Arcangelo et al. (Nature 374 : 719-723, 1995), much progresses have occurred in this field. The reelin gene encodes an extracellular protein that is crucial for neuronal migration. During the embryogenesis, reelin is expressed in the cerebral cortex in Cajal-Retzius cells and in the cerebellar cortex in outer granule cells. Although non-laminated structures such as facial nucleus, inferior olivary complex, and dorsal cochlear nucleus are also cytoarchtectually 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 the cytoarchitectonic abnormality in the facial nucleus of the reeler mouse. The branchiomotor neurons in the facial nucleus are born in the ventricular zone of the floor of the fourth ventricle, migr
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ate ventrolaterally, and finally settle near by the ventral surface of the hindbrain. Time schedules for the generation, axon formation and migration of facial motoneurons are similar both in normal and reeler mouse, but the reeler phenotype becomes identifiable at the end of neuronal migration. Although the reason why the facial nucleus is cytoarchitecually abnormal in the reeler mouse, such a long migration of the facial motoneurons seems to be more susceptible to Reelin in the reeler mouse than in the normal control. In spite of cytoarcitectual abnormality, retrograde horseradish peroxidase (HRP) study confirmed that musculotopic arrangements within the facial nucleus of the reeler mouse are still preserved, suggesting neuronal migration/rearrangement and target recognition are independently regulated.
More recently, other kinds of reeler-like mutants have been known (yotari, scrambler, SRK). Among these, yotari and scrambler mice arises from mutations in mdab1, a mouse gene related to the Drosophila gene disabled (dab). More than 10 years ago, an autosomal recessive rat mutant, shaking rat Kawasaki (SRK), has been described that exhibits a phenotype identical to reeler, but the gene responsible for this rat mutation has remained unknown. Very interestingly, the facial nucleus is cytoarchitectually more deranged in yotari and SRK compared to the normal counterparts. The reason why yotari exhibits a phenotype identical to reeler in the laminated structures but not in non-laminates structures such as the facial nucleus has remained obscure, suggesting mDab1 and Reelin proteins function as signaling molecules in a different way between non-laminated and laminated structures. Less
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