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Transgenic disruption of CRE-mediate...

Brodie, Christopher Ryan.

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Transgenic disruption of CRE-mediated gene expression in cerebellar Purkinje cells: Molecular, cellular, and behavioral consequences.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Transgenic disruption of CRE-mediated gene expression in cerebellar Purkinje cells: Molecular, cellular, and behavioral consequences./
Author:	Brodie, Christopher Ryan.
Description:	122 p.
Notes:	Major Advisers: Harry T. Orr; Linda M. Boland.
Contained By:	Dissertation Abstracts International62-11B.
Subject:	Biology, Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3034439
ISBN:	0493470557

Transgenic disruption of CRE-mediated gene expression in cerebellar Purkinje cells: Molecular, cellular, and behavioral consequences.
Brodie, Christopher Ryan.

Transgenic disruption of CRE-mediated gene expression in cerebellar Purkinje cells: Molecular, cellular, and behavioral consequences. - 122 p.

Major Advisers: Harry T. Orr; Linda M. Boland.

Thesis (Ph.D.)--University of Minnesota, 2002.

The cyclic AMP response element binding (CREB) transcription factor mediates changes in synapse strength, including those changes required for learning or development. Evidence from invertebrates suggests that CREB overexpression results in enhanced synapse modification and memory formation. The role of CREB in the mammalian cerebellum is unknown, although it is hypothesized to be required for motor learning and growth factor response during development.

ISBN: 0493470557Subjects--Topical Terms:

1017730
Biology, Genetics.

Transgenic disruption of CRE-mediated gene expression in cerebellar Purkinje cells: Molecular, cellular, and behavioral consequences.
LDR:03128nam 2200313 a 45 001 927210
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008 110425s2002 eng d
020 $a 0493470557
035 $a (UnM)AAI3034439
035 $a AAI3034439
040 $a UnM $c UnM
100 1 $a Brodie, Christopher Ryan. $3 1250760
245 1 0 $a Transgenic disruption of CRE-mediated gene expression in cerebellar Purkinje cells: Molecular, cellular, and behavioral consequences.
300 $a 122 p.
500 $a Major Advisers: Harry T. Orr; Linda M. Boland.
500 $a Source: Dissertation Abstracts International, Volume: 62-11, Section: B, page: 4912.
502 $a Thesis (Ph.D.)--University of Minnesota, 2002.
520 $a The cyclic AMP response element binding (CREB) transcription factor mediates changes in synapse strength, including those changes required for learning or development. Evidence from invertebrates suggests that CREB overexpression results in enhanced synapse modification and memory formation. The role of CREB in the mammalian cerebellum is unknown, although it is hypothesized to be required for motor learning and growth factor response during development.
520 $a To examine the role of CREB in the cerebellum, I generated transgenic mice that overexpress CREB or its inhibitor ICER (the inducible cAMP early repressor) in the Purkinje cells, a critical storage site for cerebellar learning. Additionally, I described a novel strain of mice carrying a CRE-lacZ reporter transgene, which served as an <italic>in vivo</italic> index of CREB activity. Unlike the invertebrate experiments, increased CREB in the mammalian brain did not enhance CRE-directed gene expression required for synaptic plasticity. By breeding the CREB or ICER mice to the reporter, it became evident that both ICER and wild-type CREB overexpression resulted in decreased CRE directed transcription. Furthermore, I observed that on a cell type-specific basis, the amount of phosphorylated (activated) CREB protein was inversely related to CRE-mediated transcription analyzed with the CRE-lacZ reporter, both in wild-type and CREB transgenic mice. Thus, cells in which phosphoCREB protein was normally high or genetically overexpressed showed low CRE activity. This relationship was shown to be valid in the cerebellum and hippocampus.
520 $a The decreased CRE transcription in CREB overexpressing Purkinje cells resulted in hyperactivity and rotarod deficits, yet the animals were proficient on the barcross test, another assay of balance and coordination. Consequently, CREB function seems to be linked to a limited subset of cerebellum-mediated behaviors. This surprising combination of deficit and facility suggests a complex role for CREB in Purkinje cell physiology and for Purkinje cells in the performance of these behavioral tasks.
590 $a School code: 0130.
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Biology, Neuroscience. $3 1017680
690 $a 0317
690 $a 0369
710 2 0 $a University of Minnesota. $3 676231
773 0 $t Dissertation Abstracts International $g 62-11B.
790 $a 0130
790 1 0 $a Boland, Linda M., $e advisor
790 1 0 $a Orr, Harry T., $e advisor
791 $a Ph.D.
792 $a 2002
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3034439