1995 Fiscal Year Final Research Report Summary
Studies on brain functions by gene replacement method.
| Project/Area Number |
05454673
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neuroscience in general
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| Research Institution | Kyushu University |
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Principal Investigator |
KATSUKI Motoya Med.Inst.Bioregulation, Professor, 生体防御医学研究所, 教授 (20051732)
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| Co-Investigator(Kenkyū-buntansha) |
GONDO Yoichi The Inst.Med.Science, Tokai Uninersity, Associate Professor, 総合医学研究所, 助教授 (40225678)
NAKAMURA Kenji Med.Inst.Bioregulation, Research Associate, 生体防御医学研究所, 助手 (90253533)
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| Project Period (FY) |
1993 – 1995
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| Keywords | Gene Targeting / Knockout Mouse / Gene Replacement / Glutamate receptor / Dopamine receptor / mGluR6 / alpha-MSH / Retina |
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| Research Abstract |
Recent advances in embryo manipulating technologies made it possible to generate the desired mutaion for elucidation of brain functions. We have generated knockout mice lacking neurotransmitter receptors. First, taking advantage of the restricted expression of metabotropic glutamate receptor subtype6 (mGluR6) in retinal ON bipolar cells, we generated knockout mice lacking mGluR6 expression. The homozygous mutnat mice showed a loss of ON responses but unchanged OFF responses to light. The mutant mice displayd no obvious changes in retinal cell organization nor in the projection of optic fibers to the brain. Furthemore, the mGluR6-deficient mice showed visual behavioral responses to light stimulation as examined by shuttle box avoidance behavior experiments using light exposure as a conditioned stimulus. The results demonstrate that mGluR6 is essential in synaptic transmission to the ON bipolar cell and that the OFF response provides an important means for transmitting visual inforamation.
Secondly, to elucidate the specific role of the dopamine D2 receptor (D2R) in the pituitary and brain, we generated D2R deficient (D2R mutant) mice using the gene targeting method. Electrophysiological studies as well as ligand binding assays show no functional D2R in mutant mice. The D2R mutant mice display a hypoacitivity and a slow movement with creeping manner. The expression of enkephalin mRNA in the striatum is increased in the mutant mice, but not that of dynorphin and substanceP.D2R mutant mice have significant darker coat color than wild type littermates and show an elevation of plasma alpha-melanocyte stimulating hormone levels. We found corresponding hyperplastic changes of intermediate lobe of the pituitary and the increased expression of proopiomelanocortin in the pituitarv in D2R mutant mice. These findings suggest that D2R plays a critical role in the dopaminergic system in the pituitary and the striatum.
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