Analysis of gene and protein expression related to cerebellar neurodegeneration in the calcium channel mutant mouse, leaner /
The leaner mouse exhibits severe ataxia, absence seizures and paroxysmal dyskinesia. The leaner mouse carries a mutation in the gene coding for the α1A subunit of P/Q-type calcium channels that mainly results in cerebellar neurodegeneration and dysfunction. Recent studies showed that absence seizure...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
2002.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=764789811&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | The leaner mouse exhibits severe ataxia, absence seizures and paroxysmal dyskinesia. The leaner mouse carries a mutation in the gene coding for the α1A subunit of P/Q-type calcium channels that mainly results in cerebellar neurodegeneration and dysfunction. Recent studies showed that absence seizures as well as inherited migraine and ataxia in humans are found to be associated with P/Q-type calcium channel mutations. To better understand cerebellar neurodegeneration and cerebellar dysfunction associated with calcium channel mutations, the molecular mechanisms of neurodegeneration and potential treatment for cerebellar ataxia were investigated. The aims of this dissertation were: (1) to analyze expression of calcium-binding proteins in the leaner cerebellum to understand how neurons modify calcium buffering systems under reduced calcium influx, (2) to analyze gene and protein expression by use of gene array analyses and two-dimensional gel electrophoresis combined with mass spectrometric protein identification to screen genes and proteins involved in neurodegeneration in the leaner cerebellum, and finally (3) to investigate the insulin-like growth factor-I (IGF-I) system and to determine the effectiveness of IGF-I on cerebellar dysfunction in the leaner mouse. The present results showed that calcium-binding protein (CaBP) expression is reduced in the leaner cerebellum. The reduction in CaBP expression affects calcium homeostasis, which in turn triggers neurodegeneration. Gene array analyses revealed that leaner granule cells undergo mitochondria-dependent apoptosis, whereas Purkinje cell death may be associated with lysosomal proteinase action. Investigation of the IGF-I system in the leaner mouse showed decreased serum and cerebellar IGF-I concentrations. IGF-I supplementation in the leaner mouse partially ameliorated cerebellar dysfunction. However, it did not rescue cerebellar neurodegeneration in the leaner mouse. |
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| Item Description: | Vita. "Major Subject: Veterinary Anatomy". |
| Physical Description: | x, 165 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references (leaves 136-158). |