Neuroscience 2002 Abstract
| Presentation Number: | 480.17 |
|---|---|
| Abstract Title: | Mouse models for Rubinstein-Taybi Syndrome: The role of the transcriptional coactivator CREB-binding protein (CBP) in synaptic plasticity. |
| Authors: |
Zhang, Z.*1
; Wotjak, C.1
; Brenz Verca, M. S.1
; Lutz, B.1
1MPI Psychiatry, Munich, Germany |
| Primary Theme and Topics |
Cognition and Behavior - Animal Cognition and Behavior -- Associative, nonassociative and skill learning & memory systems |
| Secondary Theme and Topics | Techniques in Neuroscience<br />- Molecular and genetic techniques |
| Session: |
480. Animal cognition and behavior: learning and memory--physiology and imaging: gene expression, transcription factors, and trophic factors Poster |
| Presentation Time: | Tuesday, November 5, 2002 8:00 AM-9:00 AM |
| Location: | Hall A2-B3 R-3 |
| Keywords: | CBP, Cre, loxP, learning and memory |
CBP (CREB-bind protein) was originally characterized as a transcriptional coactivator of CREB (cAMP response element-binding protein). CREB has been implicated in many forms of synaptic plasticity and shown to be critical for memory consolidation. Mutations of CBP were found in the human genetic disease Rubinstein-Taybi Syndrome (RTS) that is characterized by skeletal abnormalities and mental retardation. To date, the function of CBP in the adult central nervous system has not been clearified yet.
Mouse lines with CBP mutations were generated using the Cre/loxP system. A deletion of exon 2 in the CREB-binding domain (CBD) results in a frame shift and, thus, to a truncated CBP protein (CBPstop523). Three mouse lines were obtained: CBD2.floxed, which can be crossed with Cre-expressing mouse lines to obtain tissue-specific CBP mutations; CBD2.floxed.neo, which might represent a hypomorphic allele due to the presence of the Neo cassette; and the conventional CBP knock-out (CBD allele). Fear conditioning tests were applied. (1) Homozygous CBD2.floxed.neo mice did not show any learning deficits, indicating that the presence of the Neo cassette did not significantly influence CBP function. (2) Homozygous CBD2 mice showed embryonic lethality. Heterozygous CBD2 mice were not viable in C57BL6/N background, but were viable in the outbred strain CD1, which displayed impaired learning behavior as evaluated in cued and contextual fear conditioning. (3) To investigate the function of CBP in various brain regions and neuronal subpopulations regarding synaptic plasticity, the line CBD2.floexed will be crossed with various Cre-expression mouse lines.
Mouse lines with CBP mutations were generated using the Cre/loxP system. A deletion of exon 2 in the CREB-binding domain (CBD) results in a frame shift and, thus, to a truncated CBP protein (CBPstop523). Three mouse lines were obtained: CBD2.floxed, which can be crossed with Cre-expressing mouse lines to obtain tissue-specific CBP mutations; CBD2.floxed.neo, which might represent a hypomorphic allele due to the presence of the Neo cassette; and the conventional CBP knock-out (CBD allele). Fear conditioning tests were applied. (1) Homozygous CBD2.floxed.neo mice did not show any learning deficits, indicating that the presence of the Neo cassette did not significantly influence CBP function. (2) Homozygous CBD2 mice showed embryonic lethality. Heterozygous CBD2 mice were not viable in C57BL6/N background, but were viable in the outbred strain CD1, which displayed impaired learning behavior as evaluated in cued and contextual fear conditioning. (3) To investigate the function of CBP in various brain regions and neuronal subpopulations regarding synaptic plasticity, the line CBD2.floexed will be crossed with various Cre-expression mouse lines.
Supported by VW Foundation
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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