Generation and characterization of hD 5 and C-terminal mutant hD 5m transgenic rats

Zhiliang Xu; Suzhen Dong; Dan Du; Nan Jiang; Peiqua Sun; Huikun Wang; Liang Yin; Xuliang Zhang; Xiaohua Cao; Xuechu Zhen; Yinghe Hu

doi:10.1016/j.brainres.2012.01.076

Generation and characterization of hD ₅ and C-terminal mutant hD _5m transgenic rats

Zhiliang Xu
, Suzhen Dong
, Dan Du
, Nan Jiang
, Peiqua Sun
, Huikun Wang
, Liang Yin
, Xuliang Zhang
, Xiaohua Cao
, Xuechu Zhen
, Yinghe Hu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Dopamine D ₁-like receptors play important roles in many brain activities such as cognition and emotion. We have generated human hD ₅ and mutant human hD ₅ (hD _5m) transgenic rats. The C-terminal juxtamembrane domain of mutant hD ₅ was identical to that of hD5 pseudogenes. The transgenes were driven by the CAMKII promoter that led the expression mainly in the cerebral cortex and hippocampus. We have used different dopamine receptor agonists to compare the pharmacological profiles of the human hD ₅ and hD _5m receptors. The results showed that they exhibited distinct pharmacological properties. Our results of pharmacological studies indicated that the C-terminal of D ₅ receptor could play important roles in agonist binding affinity. Hippocampal long-term potentiation (LTP) evoked by tetanic stimulation was significantly reduced in both transgenic rats. In addition, we found that the overexpression of dopamine hD ₅ and hD _5m receptors in the rat brain resulted in memory impairments. Interestingly, an atypical D ₁-like receptor agonist, SKF83959, could induce anxiety in hD _5m receptor transgenic rats but had no effect on the anxiety-like behavior in D ₅ receptor transgenic and wild-type rats.

Original language	English
Pages (from-to)	27-41
Number of pages	15
Journal	Brain Research
Volume	1448
DOIs	https://doi.org/10.1016/j.brainres.2012.01.076
State	Published - 11 Apr 2012
Externally published	Yes

Keywords

D -like dopamine receptor
LTP
Learning and memory
Transgenic rat

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10.1016/j.brainres.2012.01.076

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title = "Generation and characterization of hD 5 and C-terminal mutant hD 5m transgenic rats",

abstract = "Dopamine D 1-like receptors play important roles in many brain activities such as cognition and emotion. We have generated human hD 5 and mutant human hD 5 (hD 5m) transgenic rats. The C-terminal juxtamembrane domain of mutant hD 5 was identical to that of hD5 pseudogenes. The transgenes were driven by the CAMKII promoter that led the expression mainly in the cerebral cortex and hippocampus. We have used different dopamine receptor agonists to compare the pharmacological profiles of the human hD 5 and hD 5m receptors. The results showed that they exhibited distinct pharmacological properties. Our results of pharmacological studies indicated that the C-terminal of D 5 receptor could play important roles in agonist binding affinity. Hippocampal long-term potentiation (LTP) evoked by tetanic stimulation was significantly reduced in both transgenic rats. In addition, we found that the overexpression of dopamine hD 5 and hD 5m receptors in the rat brain resulted in memory impairments. Interestingly, an atypical D 1-like receptor agonist, SKF83959, could induce anxiety in hD 5m receptor transgenic rats but had no effect on the anxiety-like behavior in D 5 receptor transgenic and wild-type rats.",

keywords = "D -like dopamine receptor, LTP, Learning and memory, Transgenic rat",

author = "Zhiliang Xu and Suzhen Dong and Dan Du and Nan Jiang and Peiqua Sun and Huikun Wang and Liang Yin and Xuliang Zhang and Xiaohua Cao and Xuechu Zhen and Yinghe Hu",

year = "2012",

month = apr,

day = "11",

doi = "10.1016/j.brainres.2012.01.076",

language = "英语",

volume = "1448",

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journal = "Brain Research",

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T1 - Generation and characterization of hD 5 and C-terminal mutant hD 5m transgenic rats

AU - Xu, Zhiliang

AU - Dong, Suzhen

AU - Du, Dan

AU - Jiang, Nan

AU - Sun, Peiqua

AU - Wang, Huikun

AU - Yin, Liang

AU - Zhang, Xuliang

AU - Cao, Xiaohua

AU - Zhen, Xuechu

AU - Hu, Yinghe

PY - 2012/4/11

Y1 - 2012/4/11

N2 - Dopamine D 1-like receptors play important roles in many brain activities such as cognition and emotion. We have generated human hD 5 and mutant human hD 5 (hD 5m) transgenic rats. The C-terminal juxtamembrane domain of mutant hD 5 was identical to that of hD5 pseudogenes. The transgenes were driven by the CAMKII promoter that led the expression mainly in the cerebral cortex and hippocampus. We have used different dopamine receptor agonists to compare the pharmacological profiles of the human hD 5 and hD 5m receptors. The results showed that they exhibited distinct pharmacological properties. Our results of pharmacological studies indicated that the C-terminal of D 5 receptor could play important roles in agonist binding affinity. Hippocampal long-term potentiation (LTP) evoked by tetanic stimulation was significantly reduced in both transgenic rats. In addition, we found that the overexpression of dopamine hD 5 and hD 5m receptors in the rat brain resulted in memory impairments. Interestingly, an atypical D 1-like receptor agonist, SKF83959, could induce anxiety in hD 5m receptor transgenic rats but had no effect on the anxiety-like behavior in D 5 receptor transgenic and wild-type rats.

AB - Dopamine D 1-like receptors play important roles in many brain activities such as cognition and emotion. We have generated human hD 5 and mutant human hD 5 (hD 5m) transgenic rats. The C-terminal juxtamembrane domain of mutant hD 5 was identical to that of hD5 pseudogenes. The transgenes were driven by the CAMKII promoter that led the expression mainly in the cerebral cortex and hippocampus. We have used different dopamine receptor agonists to compare the pharmacological profiles of the human hD 5 and hD 5m receptors. The results showed that they exhibited distinct pharmacological properties. Our results of pharmacological studies indicated that the C-terminal of D 5 receptor could play important roles in agonist binding affinity. Hippocampal long-term potentiation (LTP) evoked by tetanic stimulation was significantly reduced in both transgenic rats. In addition, we found that the overexpression of dopamine hD 5 and hD 5m receptors in the rat brain resulted in memory impairments. Interestingly, an atypical D 1-like receptor agonist, SKF83959, could induce anxiety in hD 5m receptor transgenic rats but had no effect on the anxiety-like behavior in D 5 receptor transgenic and wild-type rats.

KW - D -like dopamine receptor

KW - LTP

KW - Learning and memory

KW - Transgenic rat

UR - https://www.scopus.com/pages/publications/84862805585

U2 - 10.1016/j.brainres.2012.01.076

DO - 10.1016/j.brainres.2012.01.076

M3 - 文章

C2 - 22386496

AN - SCOPUS:84862805585

SN - 0006-8993

VL - 1448

SP - 27

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JO - Brain Research

JF - Brain Research

ER -

Generation and characterization of hD ₅ and C-terminal mutant hD _5m transgenic rats

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