| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
|
|---|
| Research Abstract |
To identify the factor responsible for the exhibition of behavioral abnormalities of BUS mice, the inner ear and the CNS of the mutant mice were examined morphologically, biochemically and molecular biologically. TEM and SEM observations showed stereociliary derangements in the sensory hair cells of the cochlear Corti's organ and picnotic features of the vestibular sensory cells in the inner ear of BUS homozygotes (bus/bus), but not heterozygotes (<plus-minus>/bus). Audiological tests revealed that BUS homozygotes were deaf in their total life. Spongiform degeneration was observed in the CNS of BUS mice, but this lesion was found from outcross and intercross experiments to be due to a gene independent of bus. A feature of hemorrhage was often found in different parts of the brain stem in BUS homozygotes at later fetal stages, but some heterozygous fetuses also had dead cells clusters in the CNS,which indicated that the hemorrage in the fetal CNS could not be accepted as a cause of abno
… More
rmal bustling hehaviors in homozygotes. Since it has been reported that Mos transgenic mice displayd behavioral abnormalities and had the inner ear defects and the spongiform degeneration in the CNS,we tested a possibility of over-expression of c-mos in BUS homozygotes by means of the ribonuclease protection assay method. The results indicated, however, that the gene was normally expreessed in the CNS of homozygotes from later fetal stages to adult stages. Thus, we had no data providing a clue in the CNS for identifying the responsible factor for BUS abnormalities at the molecular level. In views of a possible functional association of the inner ear organs with behaviors in mice, the behaviors of chemically labyrinthectomized mice were examined compared with those of BUS homozygotes. As a result, both were found very similar in behaviors, suggesting that the inner ear defects, even if no lesions exist in the CNS,elicit abnormal behaviors in mice, including circling, head shaking, and hyperkinesia. We have developed in this study three hybridoma lines, each secreting an antibody recognizing specific cells in the inner ear organs : Y10F2 recognizing the vestibular supporting cells ; H3E11 recognizing the supporting cells of the macullae and the basal supporting cells of the cristae : and Y7E3 recognizing the supporting cells of the Corti's organ. Among these, monoclonal antibody Y10F2 was found to be useful for seeking the factor responsible for BUS abnormalities, providing the data that the immunoreactivity of cells of the inner ear organs and Y10F2 (stainability) was different between homozygotes and heterozygotes, at later fetal stages. Finally, efforts are being made to identify the responsible gene, bus. For this, several species of transcripts have been so far identified as quantitatively different between the inner ear of homozygotes and that of heterozygotes, as revealed by the method of mRNA differential displa Less
|
