title: Generation and characterization of hD5 and C-terminal Mutant hD(5m) transgenic rats.
abstract: Dopamine D1-like receptors play important roles in many brain activities such as cognition and emotion. We have generated human hD5 and mutant human hD5 (hD(5m)) transgenic rats. The C-terminal juxtamembrane domain of mutant hD5 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 hD5 and hD(5m) receptors. The results showed that they exhibited distinct pharmacological properties. Our results of pharmacological studies indicated that the C-terminal of D5 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 hD5 and hD(5m) receptors in the rat brain resulted in memory impairments. Interestingly, an atypical D1-like receptor agonist, SKF83959, could induce anxiety in hD(5m) receptor transgenic rats but had no effect on the anxiety-like behavior in D5 receptor transgenic and wild-type rats.
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, PR China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Xu
authors.forename: Suzhen
authors.initials: S
authors.lastname: Dong
authors.forename: Dan
authors.initials: D
authors.lastname: Du
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.forename: Peiqua
authors.initials: P
authors.lastname: Sun
authors.forename: Huikun
authors.initials: H
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Yin
authors.forename: Xuliang
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Cao
authors.forename: Xuechu
authors.initials: X
authors.lastname: Zhen
authors.forename: Yinghe
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000523:psychology; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004558:Electric Stimulation; D055724:Electrophysiological Phenomena; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D057809:HEK293 Cells; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000523:psychology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D016548:Prosencephalon / Q000502:physiology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D050641:Receptors, Dopamine D5 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein; D050641:Receptors, Dopamine D5; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases