Mice Deficient in Golf Are Anosmic

Belluscio, Leonardo; Gold, Geoffrey H.; Nemes, Adrianna; Axel, Richard

doi:10.1016/s0896-6273(00)80435-3

Cited by 499 publications

(379 citation statements)

References 95 publications

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“…In contrast with D1R or Gaolf knockout mice that display severe phenotypes including decreased weight, postnatal mortality after birth or weaning, and spontaneous hyperlocomotor activity (Belluscio et al, 1998 heterozygous mice were apparently similar to wild-type mice. Both Drd1a + /À and Gnal + /À mice grew normally, had a normal body weight (Table 1) and were fertile (data not shown).…”

Section: D-amph-induced Glur1 Phosphorylation Is Decreased In Gaolf Bmentioning

confidence: 74%

“…Similarly, mice with a disrupted Gnal gene were produced by Belluscio et coll. (Department of biochemistry and molecular biophysics, Columbia University, New York; Belluscio et al (1998)) and backcrossed in our laboratory for up to eight generations with C57BL/6J mice to obtain homozygous (GnalÀ/À) and (Gnal + /À) heterozygous mice as well as their control littermates (Gnal + / + ). For comparing heterozygous mutant and wild-type mice, 8-week-old male mice were used for biochemical experiments while both male (2/3) and female (1/3) of 8-week-old mice were used in behavioral experiments.…”

Section: Animalsmentioning

confidence: 99%

“…For comparing heterozygous mutant and wild-type mice, 8-week-old male mice were used for biochemical experiments while both male (2/3) and female (1/3) of 8-week-old mice were used in behavioral experiments. As Gnal/-mice have an increased mortality rate after weaning (Belluscio et al, 1998), GnalÀ/À mice and their control littermates (Gnal + / + and Gnal + /À) were used 4 weeks after birth. Animals were kept in stable conditions of temperature (221C) and humidity (60%) with a constant cycle of 12 h light and 12 h dark and had free access to food and water.…”

Section: Animalsmentioning

confidence: 99%

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Quantitative Changes in Gαolf Protein Levels, but not D1 Receptor, Alter Specifically Acute Responses to Psychostimulants

Corvol

Valjent

Pascoli

et al. 2006

Neuropsychopharmacol

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Striatal dopamine D1 receptors (D1R) are coupled to adenylyl cyclase through Gaolf. Although this pathway is involved in important brain functions, the consequences of quantitative alterations of its components are not known. We explored the biochemical and behavioral responses to cocaine and D-amphetamine (D-amph) in mice with heterozygous mutations of genes encoding D1R and Gaolf (Drd1a + /À and Gnal + /À), which express decreased levels of the corresponding proteins in the striatum. Dopamine-stimulated cAMP production in vitro and phosphorylation of AMPA receptor GluR1 subunit in response to D-amph in vivo were decreased in Gnal + /À, but not Drd1a + /À mice. Acute locomotor responses to D1 agonist SKF81259, D-amph and cocaine were altered in Gnal + /À mice, and not in Drd1a + /À mice. This haploinsufficiency showed that Gaolf but not D1R protein levels are limiting for D1R-mediated biochemical and behavioral responses. Gnal + /À mice developed pronounced locomotor sensitization and conditioned locomotor responses after repeated injections of D-amph (2 mg/kg) or cocaine (20 mg/kg). They also developed normal D-amph-conditioned place preference. The D1R/cAMP pathway remained blunted in repeatedly treated Gnal + /À mice. In contrast, D-amph-induced ERK activation was normal in the striatum of these mice, possibly accounting for the normal development of long-lasting behavioral responses to psychostimulants. Our results clearly dissociate biochemical mechanisms involved in acute and delayed behavioral effects of psychostimulants. They identify striatal levels of Gaolf as a key factor for acute responses to psychostimulants and suggest that quantitative alterations of its expression may alter specific responses to drugs of abuse, or possibly other behavioral responses linked to dopamine function.

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Section: D-amph-induced Glur1 Phosphorylation Is Decreased In Gaolf Bmentioning

confidence: 74%

Section: Animalsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

See 1 more Smart Citation

Quantitative Changes in Gαolf Protein Levels, but not D1 Receptor, Alter Specifically Acute Responses to Psychostimulants

Corvol

Valjent

Pascoli

et al. 2006

Neuropsychopharmacol

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“…This is the first report demonstrating that centrally derived, voltage-gated activity alters refinement of connections to central targets and simultaneously reduces peripheral OSNs. In other loss of function studies, two key olfactory signal transduction proteins, the CNG channel and the G-protein G olf , were not required for generating synaptic specificity in the olfactory bulb (Belluscio et al, 1998;Lin et al, 2000). In the CNG-null animals, the interpretation that odorant-evoked activity does not influence axonal projections is somewhat muddled by the new finding that these mice are not completely anosmic, as initially reported (Brunet et al, 1996), and respond behaviorally (olfactometer), electrically (electro-oculography [EOG]), and cellularly (cfos activity) quite well to odorants that are classified as pheromone-like compounds (heptanone and 2,3-dimethylpyrazine [DMP]; Lin et al, 2006Lin et al, , 2007.…”

Section: Discussionmentioning

confidence: 91%

Deletion of voltage‐gated channel affects glomerular refinement and odorant receptor expression in the mouse olfactory system

Biju

Marks

Mast

et al. 2007

J of Comparative Neurology

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Olfactory sensory neurons (OSNs) expressing a specific odorant receptor (OR) gene send axonal projections to specific glomeruli, creating a stereotypic olfactory sensory map. Odorant receptor sequence, G-protein cAMP signaling, and axon guidance molecules have been shown to direct axons of OSNs toward central targets in the olfactory bulb (OB). Although the OR sequence may act as one determinant, our objective was to elucidate the extent by which voltage-dependent activity of postsynaptic projection neurons in the OB centrally influences peripheral development and target destination of OSNs. We bred OR-tagged transgenic mice to homozygosity with mice that had a gene-targeted deletion of the Shaker potassium ion channel (Kv1.3) to elucidate how activity modulates synaptic connections that formulate the sensory map. Here we report that the Kv1.3 ion channel, which is predominantly expressed in mitral cells and whose gene-targeted deletion causes a "super-smeller" phenotype, alters synaptic refinement of axonal projections from OSNs expressing P2, M72, and MOR28 ORs. Absence of Kv1.3 voltage-gated activity caused the formation of small, heterogeneous, and supernumerary glomeruli that failed to undergo neural pruning over development. These changes were accompanied by a significant decrease in the number of P2-, M72-, and MOR28-expressing OSNs, which contained an overexpression of OR protein and G-protein G olf in the cilia of the olfactory epithelium. These findings suggest that voltage-gated activity of projection neurons is essential to refine primary olfactory projections and that it regulates proper expression of the transduction machinery at the periphery. Indexing termsolfactory coding; axon targeting; olfaction; odorant receptor; Kv1.3The development of precise connectivity and maintenance of an olfactory sensory map is thought to rely upon guidance molecules that are recognized by receptors on olfactory sensory neurons (OSNs) or that are regulated by G-protein-mediated cAMP signals (Bozza et al., 2002;St John et al., 2002;Imai et al., 2006; Lattermann et al., 2007;Sweeney et al., 2007). OSNs expressing a given olfactory receptor are primarily randomly dispersed within one of four zones in the main olfactory epithelium (Ressler et al., 1993;Vassar et al., 1993;Mombaerts et al., 1996) but send their axonal projections to spatially conserved glomeruli within the olfactory bulb (Mombaerts, 1996;Wang et al., 1998;Tsuboi et al., 1999). Thus the olfactory bulb (OB) serves as a two- NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript dimensional map of receptor activation to provide the neural code to discriminate olfactory sensory information (Yu et al., 2004). Odorant quality is thus encoded by a specific combination of activated glomeruli (Mori et al., 1999;Strotmann et al., 2000), and the formation of glomeruli depends on contextual sorting of axons expressing like OR proteins (Belluscio et al., 2002;Mombaerts, 2006).If contextual cues from adjacent homotypic interactions initiate...

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“…This is further supported by the locomotor behaviour of the mice deficient for Gα olf . When tested in open field exercises, the GNAL+/− mice exhibit a slight decrease in basal locomotor activity, while the −/− mice display locomotor hyperactivity (Belluscio et al, 1998;Schwindinger et al, 2003) similar to a D1 knockout (Xu et al, 1994a,b).…”

Section: Introductionmentioning

confidence: 99%

Investigation of the G protein subunit Gαolf gene (GNAL) in attention deficit/hyperactivity disorder

Laurin

Ickowicz

Pathare

et al. 2008

Journal of Psychiatric Research

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The dopamine system plays an important role in the regulation of attention and motor behavior, subsequently, several dopamine-related genes have been associated with Attention Deficit/ Hyperactivity Disorder (ADHD). Among them are the dopamine receptors D1 and D5 that mediate adenylyl cyclase activation through coupling with G s -like proteins. We thus hypothesized that the G s -like subunit Gα olf , expressed in D1-rich areas of the brain, contributes to the genetic susceptibility of ADHD. To evaluate the involvement of the Gα olf gene, GNAL, in ADHD, we examined the inheritance pattern of 12 GNAL polymorphisms in 258 nuclear families ascertained through a proband with ADHD (311 affected children) using the transmission/disequilibrium test (TDT). Categorical analysis of individual marker alleles demonstrated biased transmission of one polymorphism in GNAL intron 3 (rs2161961; P = 0.011). We also observed significant relationships between rs2161961 and dimensional symptoms of inattention and hyperactivity/ impulsivity (P = 0.003 and P = 0.008). In addition, because of recent evidence of imprinting at the GNAL locus, secondary analyses were split into maternal and paternal transmissions to assess a contribution of parental effects. We found evidence of strong maternal effect, with preferential transmission of maternal alleles for rs2161961A (P = 0.005) and rs8098539A (P = 0.035). These preliminary findings suggest a possible contribution of GNAL in the susceptibility to ADHD, with possible involvement of parent-of-origin effects.

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Mice Deficient in Golf Are Anosmic

Cited by 499 publications

References 95 publications

Quantitative Changes in Gαolf Protein Levels, but not D1 Receptor, Alter Specifically Acute Responses to Psychostimulants

Quantitative Changes in Gαolf Protein Levels, but not D1 Receptor, Alter Specifically Acute Responses to Psychostimulants

Deletion of voltage‐gated channel affects glomerular refinement and odorant receptor expression in the mouse olfactory system

Investigation of the G protein subunit Gαolf gene (GNAL) in attention deficit/hyperactivity disorder

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