Conditional inactivation of the dopamine receptor 5 gene: Flanking the <i>Drd5</i> gene with loxP sites

Heyer, Joerg; Xiao, Qingqing; Bugaj-Gaweda, Bozena; Ramboz, Sylvie; Unterbeck, A.

doi:10.1002/gene.10069

Cited by 4 publications

(1 citation statement)

References 8 publications

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“…The absence of any selective D 5 antagonist means that acute pharmacological blockade of D 5 receptors in adulthood cannot be compared with their developmental absence. However, the recent generation of a conditional D 5 knockout (Heyer et al, 2002), which allows temporal control over endogenous D 5 receptor expression, has the potential to be informative in this regard. Irrespective of these considerations, the ability to distinguish discrete functional roles among individual members of the D 1 -like receptor subfamily, through systematic comparison of congenic D 5 and D 1 mutants, highlights the complexity of DAergic signaling, and may have important therapeutic implications.…”

Section: Receptors and Behavioural Regulationmentioning

confidence: 99%

Ethological resolution of behavioural topography and D₁‐like versus D₂‐like agonist responses in congenic D₅ dopamine receptor mutants: Identification of D₅:D₂‐like interactions

O’Sullivan

Kinsella²,

Sibley

et al. 2005

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The phenotypic ethogram of congenic dopamine D(5) receptor "knockout" mice was evaluated. Each individual topography of behaviour within the natural repertoire was assessed over the extended course of initial exploration of and subsequent habituation to the environment, and following challenge with a series of D(1)-like agonists. Over initial exploration, D(5)-null mice evidenced a modest reduction in locomotion and a modest increase in sifting. Subsequent habituation revealed additional phenotypic effects, primarily overall reduction in grooming and delayed habituation of rearing. Among D(1)-like agonists, A 68930 stimulates both adenylyl cyclase and a putative D(1)-like receptor coupled to stimulation of phospholipase C-mediated phosphoinositide hydrolysis; conversely, SK&F 83959 stimulates phosphoinositide hydrolysis but not adenylyl cyclase while SK&F 83822 stimulates adenylyl cyclase but not phosphoinositide hydrolysis. Though programmed grooming syntax and episodic seizure activity induced by A 68930 and SK&F 83822 were unaltered, grooming induced by SK&F 83959 was reduced in D(5) mutants. Stereotyped, ponderous locomotion induced by the D(2)-like agonist RU 24213 was enhanced in D(5) mutants. Phenotypic and pharmacological characterisation of congenic D(5)-null mice at an ethological level identifies novel functional roles for the D(5) receptor in mediating discrete topographies of behaviour relating to exploration, sequential motor coordination, and how these processes change over the course of interaction with and habituation to the environment. Additionally, they indicate the involvement of phosphoinositide hydrolysis and D(5):D(2)-like interactions in regulating these processes.

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Section: Receptors and Behavioural Regulationmentioning

confidence: 99%

Ethological resolution of behavioural topography and D₁‐like versus D₂‐like agonist responses in congenic D₅ dopamine receptor mutants: Identification of D₅:D₂‐like interactions

O’Sullivan

Kinsella²,

Sibley

et al. 2005

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Conditional Mutagenesis of G-Protein Coupled Receptors and G-Proteins

Offermanns

Conditional Mutagenesis: An Approach to Disease Models

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The G-protein-coupled receptor signaling system, consisting of a huge variety of receptors as well as of many G-proteins and effectors, operates in every cell and is involved in many physiological and pathological processes. The versatility of this system and the involvement of specific components makes G-protein-coupled receptors and their signaling pathways ideal targets for pharmacological interventions. Classical mouse knockout models have often provided important preliminary insights into the biological roles of individual receptors and signaling pathways and they are routinely used in the process of target validation. The recent development of efficient conditional mutagenesis techniques now allows a much more detailed analysis of G-protein-mediated signaling transduction processes. This review summarizes some of the areas in which progress has recently been made by applying conditional mutagenesis of genes coding for G-proteins and G-protein-coupled receptors.

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Phenotypic analysis of dopamine receptor knockout mice; recent insights into the functional specificity of dopamine receptor subtypes

Lachowicz²,

2004

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Conditional inactivation of the dopamine receptor 5 gene: Flanking the Drd5 gene with loxP sites

Cited by 4 publications

References 8 publications

Ethological resolution of behavioural topography and D₁‐like versus D₂‐like agonist responses in congenic D₅ dopamine receptor mutants: Identification of D₅:D₂‐like interactions

Ethological resolution of behavioural topography and D₁‐like versus D₂‐like agonist responses in congenic D₅ dopamine receptor mutants: Identification of D₅:D₂‐like interactions

Conditional Mutagenesis of G-Protein Coupled Receptors and G-Proteins

Phenotypic analysis of dopamine receptor knockout mice; recent insights into the functional specificity of dopamine receptor subtypes

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Conditional inactivation of the dopamine receptor 5 gene: Flanking the Drd5 gene with loxP sites

Cited by 4 publications

References 8 publications

Ethological resolution of behavioural topography and D1‐like versus D2‐like agonist responses in congenic D5 dopamine receptor mutants: Identification of D5:D2‐like interactions

Ethological resolution of behavioural topography and D1‐like versus D2‐like agonist responses in congenic D5 dopamine receptor mutants: Identification of D5:D2‐like interactions

Conditional Mutagenesis of G-Protein Coupled Receptors and G-Proteins

Phenotypic analysis of dopamine receptor knockout mice; recent insights into the functional specificity of dopamine receptor subtypes

Contact Info

Product

Resources

About

Ethological resolution of behavioural topography and D₁‐like versus D₂‐like agonist responses in congenic D₅ dopamine receptor mutants: Identification of D₅:D₂‐like interactions

Ethological resolution of behavioural topography and D₁‐like versus D₂‐like agonist responses in congenic D₅ dopamine receptor mutants: Identification of D₅:D₂‐like interactions