Targeted gene expression in dopamine and serotonin neurons of the mouse brain

Zhuang, Xiaoxi; Masson, Justine; Gingrich, Jay A.; Rayport, Stephen; Hen, René

doi:10.1016/j.jneumeth.2004.09.020

Cited by 261 publications

(279 citation statements)

References 28 publications

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“…The SERT cre mouse line has been described previously (Zhuang et al, 2005). This is a gene trap construction, which replaces exon 14 of the serotonin transporter gene (SERT) with a gene sequence encoding cre-recombinase.…”

Section: Animalsmentioning

confidence: 99%

“…This is a gene trap construction, which replaces exon 14 of the serotonin transporter gene (SERT) with a gene sequence encoding cre-recombinase. Previous studies have shown that recombination occurs by E12 in the raphe neurons (Narboux-Neme et al, 2008) and that virtually all tryptophan hydroxylase 2 (TPH2) neurons in the raphe have recombined in postnatal life (Zhuang et al, 2005). Male VMAT2 lox/ + :: SERT cre/ + or VMAT2 lox/lox :: SERT cre/ + mice were mated with female VMAT2 lox/lox to generate the three genotypes that were analyzed: VMAT2 lox/lox ::SERT cre/ + (recombined), VMAT2 lox/lox (control 1), and VMAT2 lox/ + :: SERT cre/ + (control 2).…”

Section: Animalsmentioning

confidence: 99%

“…These mice were crossed to a previously described mouse line in which the 5-HT transporter (SERT, Slc6a4) promoter drives the expression of bacterial Cre recombinase (Narboux-Neme et al, 2008;Zhuang et al, 2005). The VMAT2 lox/lox :: SERT cre/ + double transgenic line (hence termed 'VMAT2 sertÀcre ') was amplified for analysis.…”

Section: Specific Invalidation Of the Vmat2 Gene In 5-ht Neuronsmentioning

confidence: 99%

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Severe Serotonin Depletion after Conditional Deletion of the Vesicular Monoamine Transporter 2 Gene in Serotonin Neurons: Neural and Behavioral Consequences

Narboux-Nême

Sagné

Doly

et al. 2011

Neuropsychopharmacol

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The vesicular monoamine transporter type 2 gene (VMAT2) has a crucial role in the storage and synaptic release of all monoamines, including serotonin (5-HT). To evaluate the specific role of VMAT2 in 5-HT neurons, we produced a conditional ablation of VMAT2 under control of the serotonin transporter (slc6a4) promoter. VMAT2 sertÀcre mice showed a major (À95%) depletion of 5-HT levels in the brain with no major alterations in other monoamines. Raphe neurons contained no 5-HT immunoreactivity in VMAT2 sertÀcre mice but developed normal innervations, as assessed by both tryptophan hydroxylase 2 and 5-HT transporter labeling. Increased 5-HT 1A autoreceptor coupling to G protein, as assessed with agonist-stimulated [ 35 S]GTP-g-S binding, was observed in the raphe area, indicating an adaptive change to reduced 5-HT transmission. Behavioral evaluation in adult VMAT2 sertÀcre mice showed an increase in escape-like reactions in response to tail suspension and anxiolytic-like response in the novelty-suppressed feeding test. In an aversive ultrasoundinduced defense paradigm, VMAT2 sertÀcre mice displayed a major increase in escape-like behaviors. Wild-type-like defense phenotype could be rescued by replenishing intracellular 5-HT stores with chronic pargyline (a monoamine oxidase inhibitor) treatment. Pargyline also allowed some form of 5-HT release, although in reduced amounts, in synaptosomes from VMAT2 sertÀcre mouse brain. These findings are coherent with the notion that 5-HT has an important role in anxiety, and provide new insights into the role of endogenous 5-HT in defense behaviors.

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Section: Animalsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Section: Specific Invalidation Of the Vmat2 Gene In 5-ht Neuronsmentioning

confidence: 99%

See 1 more Smart Citation

Severe Serotonin Depletion after Conditional Deletion of the Vesicular Monoamine Transporter 2 Gene in Serotonin Neurons: Neural and Behavioral Consequences

Narboux-Nême

Sagné

Doly

et al. 2011

Neuropsychopharmacol

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“…The D1R cre (founder line EY262), D2R cre (founder line ER44), and A2AR cre (founder line KG139) bacterial artificial chromosome (BAC) transgenic mouse lines were purchased from GENSAT (The Rockefeller University). The DAT cre knock-in mouse line was obtained from Dr Xiaoxi Zhuang (University of Chicago, Chicago, IL) and has been previously published (Zhuang et al, 2005). Experimental animals were obtained by crossing homozygous floxed Grk2 (129/C57BL/6J) mice to homozygous floxed mice that were also hemizygous (from BAC transgenic lines) or heterozygous (for the knock-in mouse line) for cre.…”

Section: Generation Of Experimental Animalsmentioning

confidence: 99%

Selective Deletion of GRK2 Alters Psychostimulant-Induced Behaviors and Dopamine Neurotransmission

Daigle

Ferris

Gainetdinov

et al. 2014

Neuropsychopharmacol

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GRK2 is a G protein-coupled receptor kinase (GRK) that is broadly expressed and is known to regulate diverse types of receptors. GRK2 null animals exhibit embryonic lethality due to a severe developmental heart defect, which has precluded the study of this kinase in the adult brain. To elucidate the specific role of GRK2 in the brain dopamine (DA) system, we used a conditional gene knockout approach to selectively delete GRK2 in DA D1 receptor (D1R)-, DA D2 receptor (D2R)-, adenosine 2A receptor (A2AR)-, or DA transporter (DAT)-expressing neurons. Here we show that select GRK2-deficient mice display hyperactivity, hyposensitivity, or hypersensitivity to the psychomotor effects of cocaine, altered striatal signaling, and DA release and uptake. Mice with GRK2 deficiency in D2R-expressing neurons also exhibited increased D2 autoreceptor activity. These findings reveal a cell-type-specific role for GRK2 in the regulation of normal motor behavior, sensitivity to psychostimulants, dopamine neurotransmission, and D2 autoreceptor function.

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“…The original heterozygous breeders acquired from Dr. Xiaoxi Zhuang at the University of Chicago were generated by standard homologous recombination techniques as described by Zhuang et al (2005). The original heterozygous mutants were created on a 129/SvJ genetic background and backcrossed to C57BL/6 mice for four generations.…”

Section: Subjectsmentioning

confidence: 99%

Marked decrease of LSD-induced stimulus control in serotonin transporter knockout mice

Krall

Richards

Rabin

et al. 2008

Pharmacology Biochemistry and Behavior

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Rationale-Based upon extensive studies in the rat, it has been suggested that stimulus control by LSD is mediated by 5-HT 2A receptors, with serotonergic receptors of the 5-HT 1A and 5-HT 2C subtypes playing modulatory roles. In genetically modified mice lacking the serotonin transporter (SERT), 5-HT 2A receptor density is decreased and, at a functional level, the head twitch response following the administration of DOI, an index of activation of 5-HT 2A receptors, is reduced. Taken together, these studies led us to hypothesize that the efficacy of LSD in establishing stimulus control is diminished or abolished in mice lacking the serotonin transporter.Objective-Determine the efficacy of LSD for establishing stimulus control in SERT knockout (KO) mice.Methods-SERT KO mice and wildtype (WT) littermates were trained in a visual discrimination on a progressive fixed ratio (FR) water-reinforced task and subsequently trained on a FR10 schedule with LSD (0.17 or 0.30 mg/kg) or vehicle. To control for general deficiencies in drug discrimination, mice were trained with pentobarbital (15 or 30 mg/kg) or vehicle.Results-The visual stimulus exerted control in both genotypes. LSD induced stimulus control in 90% of WT mice but only 31% of SERT KO mice. In contrast, pentobarbital induced stimulus control in 80% of WT mice and 54% of knockout mice.Conclusions-Although SERT KO mice exhibited stimulus control by the non-serotonergic drug, pentobarbital, the efficacy of LSD in these animals was markedly decreased, suggesting that reduced density of 5-HT 1A and/or 5-HT 2A receptors underlies the absence of stimulus control by LSD.

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Targeted gene expression in dopamine and serotonin neurons of the mouse brain

Cited by 261 publications

References 28 publications

Severe Serotonin Depletion after Conditional Deletion of the Vesicular Monoamine Transporter 2 Gene in Serotonin Neurons: Neural and Behavioral Consequences

Severe Serotonin Depletion after Conditional Deletion of the Vesicular Monoamine Transporter 2 Gene in Serotonin Neurons: Neural and Behavioral Consequences

Selective Deletion of GRK2 Alters Psychostimulant-Induced Behaviors and Dopamine Neurotransmission

Marked decrease of LSD-induced stimulus control in serotonin transporter knockout mice

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