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TA1 receptor

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Target id: 364

Nomenclature: TA1 receptor

Family: Trace amine receptor

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 339 6q23.2 TAAR1 trace amine associated receptor 1 6,8
Mouse 7 332 10 A4 Taar1 trace amine-associated receptor 1 8
Rat 7 332 1p12 Taar1 trace-amine-associated receptor 1 6,46
Previous and Unofficial Names Click here for help
TAR1 | TaR-1 | trace amine receptor 1 | TRAR1
Database Links Click here for help
Specialist databases
GPCRdb taar1_human (Hs), taar1_mouse (Mm), taar1_rat (Rn)
Other databases
Alphafold Q96RJ0 (Hs), Q923Y8 (Mm), Q923Y9 (Rn)
ChEMBL Target CHEMBL5857 (Hs), CHEMBL4908 (Mm), CHEMBL3833 (Rn)
DrugBank Target Q96RJ0 (Hs)
Ensembl Gene ENSG00000146399 (Hs), ENSMUSG00000056379 (Mm), ENSRNOG00000016073 (Rn)
Entrez Gene 134864 (Hs), 111174 (Mm), 113914 (Rn)
Human Protein Atlas ENSG00000146399 (Hs)
KEGG Gene hsa:134864 (Hs), mmu:111174 (Mm), rno:113914 (Rn)
OMIM 609333 (Hs)
Pharos Q96RJ0 (Hs)
RefSeq Nucleotide NM_138327 (Hs), NM_053205 (Mm), NM_134328 (Rn)
RefSeq Protein NP_612200 (Hs), NP_444435 (Mm), NP_599155 (Rn)
UniProtKB Q96RJ0 (Hs), Q923Y8 (Mm), Q923Y9 (Rn)
Wikipedia TAAR1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-EM structure of the methamphetamine-TA1 receptor complex
PDB Id:  8W87
Ligand:  methamphetamine
Resolution:  2.8Å
Species:  Human
References:  31
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-EM structure of the RO5256390-TA1 receptor complex
PDB Id:  8W8A
Ligand:  RO5256390
Resolution:  2.8Å
Species:  Human
References:  31
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-EM structure of the SEP-363856-bound TA1 receptor-Gs complex
PDB Id:  8W88
Ligand:  ulotaront
Resolution:  2.6Å
Species:  Human
References:  31
Natural/Endogenous Ligands Click here for help
dopamine
3-iodothyronamine
octopamine
β-phenylethylamine
tyramine
Comments: Tyramine is the most potent endogenous agonist
Potency order of endogenous ligands
tyramine > β-phenylethylamine > octopamine = dopamine  [6]

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]tyramine Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Full agonist 7.7 pKd 6
⤷ pKd 7.7 (Kd 2x10-8 M) [6]
RO5166017 Small molecule or natural product Mm Partial agonist 8.7 pKi 49
⤷ pKi 8.7 (Ki 1.9x10-9 M) [49]
RO5166017 Small molecule or natural product Rn Full agonist 8.6 pKi 49
⤷ pKi 8.6 (Ki 2.7x10-9 M) [49]
RO5166017 Small molecule or natural product Hs Full agonist 7.5 pKi 49
⤷ pKi 7.5 (Ki 3.1x10-8 M) [49]
tyramine Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 7.2 pKi 7
⤷ pKi 7.2 (Ki 7x10-8 M) [7]
tyramine Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Mm Agonist 6.4 pKi 7
⤷ pKi 6.4 (Ki 4.04x10-7 M) [7]
RO5166017 Small molecule or natural product Mm Partial agonist 8.5 pEC50 49
⤷ pEC50 8.5 (EC50 3.3x10-9 M) [49]
RO5166017 Small molecule or natural product Rn Full agonist 7.9 pEC50 49
⤷ pEC50 7.9 (EC50 1.4x10-8 M) [49]
3-iodothyronamine Small molecule or natural product Ligand is endogenous in the given species Rn Full agonist 7.5 – 7.9 pEC50 22,52,60
⤷ pEC50 7.5 – 7.9 [22,52,60]
dexamfetamine Small molecule or natural product Approved drug Ligand has a PDB structure Mm Full agonist 6.7 – 8.7 pEC50 46,63
⤷ pEC50 6.7 – 8.7 [46,63]
RO5166017 Small molecule or natural product Hs Full agonist 7.3 pEC50 49
⤷ pEC50 7.3 (EC50 5.5x10-8 M) [49]
ralmitaront Small molecule or natural product Ligand has a PDB structure Hs Agonist 7.2 pEC50 19
⤷ pEC50 7.2 (EC50 5.85x10-8 M) [19]
tyramine Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 6.9 – 7.2 pEC50 7-8,46
⤷ pEC50 6.9 – 7.2 [7-8,46]
β-phenylethylamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Mm Full agonist 6.3 – 7.4 pEC50 23,46,63
⤷ pEC50 6.3 – 7.4 [23,46,63]
3-iodothyronamine Small molecule or natural product Ligand is endogenous in the given species Mm Full agonist 6.5 – 7.0 pEC50 22,52,60
⤷ pEC50 6.5 – 7.0 [22,52,60]
2-phenyl-propylamine Small molecule or natural product Hs Agonist 6.5 – 7.0 pEC50 61
⤷ pEC50 6.5 – 7.0 (EC50 3.25x10-7 – 1.04x10-7 M) [61]
tyramine Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Mm Full agonist 6.2 – 7.1 pEC50 7,23,46,63
⤷ pEC50 6.2 – 7.1 [7,23,46,63]
β-phenylethylamine Small molecule or natural product Ligand is endogenous in the given species Hs Full agonist 6.2 – 7.0 pEC50 5-6,23-24,28,61
⤷ pEC50 6.2 – 7.0 [5-6,23-24,28,61]
R(-)amphetamine Small molecule or natural product Ligand has a PDB structure Rn Partial agonist 6.5 – 6.7 pEC50 8,46
⤷ pEC50 6.5 – 6.7 [8,46]
β-phenylethylamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Rn Full agonist 6.4 – 6.6 pEC50 8,46
⤷ pEC50 6.4 – 6.6 [8,46]
dexamfetamine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.0 – 6.9 pEC50 5,27
⤷ pEC50 6.0 – 6.9 [5,27]
R(-)amphetamine Small molecule or natural product Ligand has a PDB structure Hs Full agonist 6.2 – 6.6 pEC50 5,27
⤷ pEC50 6.6 [5]
pEC50 6.2 (EC50 6x10-7 M) [27]
R(-)amphetamine Small molecule or natural product Ligand has a PDB structure Mm Full agonist 5.3 – 7.2 pEC50 46,63
⤷ pEC50 5.3 – 7.2 [46,63]
dexamfetamine Small molecule or natural product Approved drug Ligand has a PDB structure Rn Full agonist 6.1 – 6.4 pEC50 8,46
⤷ pEC50 6.1 – 6.4 [8,46]
tyramine Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 5.8 – 6.7 pEC50 5-7,23-24,61
⤷ pEC50 5.8 – 6.7 [5-7,23-24,61]
octopamine Small molecule or natural product Rn Full agonist 5.9 pEC50 8
⤷ pEC50 5.9 [8]
octopamine Small molecule or natural product Mm Full agonist 5.4 – 5.8 pEC50 23,63
⤷ pEC50 5.4 – 5.8 [23,63]
octopamine Small molecule or natural product Hs Full agonist 4.8 – 5.8 pEC50 5-6,23-24,61
⤷ pEC50 4.8 – 5.8 [5-6,23-24,61]
ractopamine Small molecule or natural product Mm Agonist 4.8 pEC50 34
⤷ pEC50 4.8 (EC50 1.6x10-5 M) [34]
Description: Measuring chloride conductance in oocytes coexpressing hCFTR and mTAAR1, as a as a sensor for intracellular cAMP modulation.
ulotaront Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 6.8 pIC50 12
⤷ pIC50 6.8 (IC50 1.4x10-7 M) [12]
RO5256390 Small molecule or natural product N/A Partial agonist - - 32
⤷ [32]
View species-specific agonist tables
Agonist Comments
There is a lack of specific agonists, which makes investigation of the TA1 receptor difficult outside of isolated expression systems. Species differences do exist, although a greater body of comparable literature is required to confirm these. Radiolabelled 3-iodothyronamine has been synthesised [39] but has not been fully characterised and is not yet commercially available.

There are two reports of selective TA1 partial agonists. (1) RO5203648. In HEK293 cells, Ki values were 6.8nM (human TA1), 1nM (rat TA1) and 0.5nM (mouse TA1). EC50 (and Emax compared to β-Phenylethylamine) values in cAMP assay were 30nM (73%) for human, 6.8nM (59%) for rat and 4nM (48%) for mouse TA1 [50]. (2) RO5073012. Ki human TA1 6nM with 140 fold selectivity for TA1 over adrenergic α2. In functional assay EC50 (Emax) values were 23nM (35%) for human TA1, 25nM (24%) for rat TA1 and 23nM (26%) for mouse TA1 [20].

More recently described partial agonists from [18,51] with improved pharmacological profiles and pharmacokinetics compared to RO5166017. These are RO5256390 ((S)-4-((S)-2-phenyl-butyl)-4,5-dihydro-oxazol-2-ylamine) with Ki binding in HEK293 cells of 4nM (mouse TA1), 1nM (rat TA1) and 24nM (human TA1) and EC50 values in cAMP assays in HEK293 cells (Emax relative to β-phenylethylamine) of 2nM (79%) (mouse TA1); 5nM (107%) (rat TA1) and 16nM (98%) (human TA1 and RO5263397 ((S)-4-(3-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine with Ki of 1nM (mouse TA1), 9nM (rat TA1) and 4nM (human TA1) and EC50 (Emax relative to β-phenylethylamine) in cAMP assays in HEK293 cells of 1nM (59%) (mouse TA1), 47nM (76%) (rat TA1) and 17nM (81%) (human TA1).

Ractopamine's agonist activity at mTA1 is completely reversed by the antagonist EPPTB [34].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
EPPTB Small molecule or natural product Mm Inverse agonist 9.0 pKi 7,56
⤷ pKi 9.0 (Ki 9x10-10 M) [7,56]
EPPTB Small molecule or natural product Rn Inverse agonist 6.0 pKi 7
⤷ pKi 6.0 (Ki 9.42x10-7 M) [7]
EPPTB Small molecule or natural product Mm Inverse agonist 7.7 pIC50 7
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [7]
EPPTB Small molecule or natural product Rn Inverse agonist 5.4 pIC50 7
⤷ pIC50 5.4 (IC50 4.5x10-6 M) [7]
EPPTB Small molecule or natural product Hs Inverse agonist 5.1 pIC50 7
⤷ pIC50 5.1 (IC50 7.487x10-6 M) [7]
View species-specific antagonist tables
Antagonist Comments
There are currently no commercially available antagonists available for the TA1 receptor, although lead compounds have been rationally synthesised but not yet fully characterised [59].

EPPTB (RO5212773) inhibited basal cAMP levels in HEK293 cells expressing human, rat and mouse TA1 receptors and has 1000 fold selectivity for the mouse TA1 receptor. EPPTB TA1 antagonism is not detected in Taar1 knockout mice [7]. In Schild analysis RO5212773 was a competitive antagonist [7].
Allosteric Modulator Comments
There are currently no known allosteric regulators of the TA1 receptor.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
Comments:  Tyramine causes an increase in intracellular cAMP in HEK293 or COS-7 cells expressing the TA1 receptor in vitro [6,8,29]. In addition, coupling to a promiscuous Gαq has been observed, resulting in increased intracellular calcium concentration [40]. In vivo transduction mechanisms have not yet been studied. In HEK293 cells expressing human, rat or mouse TA1 the receptor is reported to exhibit constitutive active as basal levels of cAMP were reduced by the TA1 selective compound RO5212773 (EPPTB) [7]. TA1 agonists (methamphetamine and β-PEA) increased intracellular cAMP levels in primary human astrocytes with TA1 knockdown significantly reducing intracellular cAMP levels in response to these agonists [10].
References:  6,8,29
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family
Comments:  RD-HGA16 cells express the promiscuous Gq protein Gα16 that allows the coupling of TA1 to the mobilisation of intracellular calcium [27-28].
References: 
Tissue Distribution Click here for help
Human pancreatic islet beta cells, duodenum and pylorus
Species:  Human
Technique:  immunohistochemistry
References:  45
CNS (region specific) & several peripheral tissues:
Stomach > amygdala, kidney, lung, small intestine > cerebellum, dorsal root ganglion, hippocampus, hypothalamus, liver, medulla oblongata, pancreas, pituitary gland, pontine reticular formation, prostate, skeletal muscle, spleen.
Species:  Human
Technique:  RT-PCR
References:  6
Circulating leukocytes of healthy subjects (upregulation occurs upon addition of phytohaemagglutinin).
Species:  Human
Technique:  RT-PCR
References:  11,41
Malignancy-derived B Cells
Species:  Human
Technique:  Western blot
References:  62
Leukocytes
Species:  Human
Technique:  RT-PCR
References:  4
Primary Tonsillar B Cells
Species:  Human
Technique:  Western blot
References:  13
Pancreatic islet β cells.
Species:  Human
Technique:  In situ hybridisation, RT-PCR
References:  47
Gastric D-Cells
Species:  Mouse
Technique:  RNA sequencing and RT-PCR
References:  2
Thyroid
Species:  Mouse
Technique:  Immunohistochemistry
References: 
Prefrontal cortical neurones
Species:  Mouse
Technique:  RT-PCR
References:  15
CNS:
Mitral cell layer of olfactory bulb, piriform cortex, arcuate, motor and mesencephalic trigeminal nuclei, lateral reticular and hypoglossal nuclei, cerebellar Purkinje cells, ventral horn of spinal cord > frontal, entorhinal and agranular cortices, ventral pallidum, thalamus, hypothalamic nuclei, hippocampus, ambiguus, dorsal raphe and gigantocellular reticular nuclei > septum, basal ganglia, amygdala, myelencephalon, dorsal horn of the spinal cord.
Species:  Mouse
Technique:  in situ hybridisation
References:  6
Substantia nigra (dopaminergic neurons).
Species:  Mouse
Technique:  Immunohistochemistry
References:  66
Brain regions associated with corticolimbic dopaminergic systems: substantia nigra/ventral tegmental area, nucleus accumbens, frontal cortex.
Species:  Mouse
Technique:  RT-PCR
References:  13
Thyroid
Species:  Rat
Technique:  Immunohistochemistry
References:  58
Cardiac ventricles.
Species:  Rat
Technique:  RT-PCR
References:  9
Aorta
Species:  Rat
Technique:  RT-PCR, Western blot
References:  17
Spinal neurones/motorneurones- adult and neonate
Species:  Rat
Technique:  PCR, in situ hybridisation, immunochemistry
References:  21
Tissue Distribution Comments
In the brain (mouse, rhesus monkey) the TA1 receptor localises to neurones within the monoaminergic pathways and there is emerging evidence for a modulatory role for TA1 on function of these systems. Co-expression of TA1 with the dopamine transporter (either within the same neurone or in adjacent neurones) implies direct/indirect modulation of CNS dopaminergic function. In cells expressing both human TA1 and a monoamine transporter (DAT, SERT or NET) signalling via TA1 is enhanced [38,64,66-67].
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of cAMP levels in HEK293 cells transfected with the human TA1 receptor.
Species:  Human
Tissue:  HEK293 cells.
Response measured:  Intracellular cAMP accumulation.
References:  29
Measurement of cAMP levels in HEK293 cells transfected with the murine TA1 receptor.
Species:  Mouse
Tissue:  HEK293 cells.
Response measured:  Intracellular cAMP accumulation.
References:  60,63
Measurement of cAMP levels in COS-7 cells transfected with the human TA1 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Intracellular cAMP accumulation.
References:  6
Measurement of the inward chloride current in Xenopus oocytes co-transfected with human TA1 and CFTR in response to tyramine.
Species:  Human
Tissue:  Xenopus laevis oocytes
Response measured:  Inward chloride current
References:  6
Fluorometry of intracellular calcium concentration in Chinese Hamster Ovary (CHO) cells expressing the promiscuous Gq, Gα16 and human TA1 receptor.
Species:  Human
Tissue:  CHO cells
Response measured:  Increase in cytopasmic calcium
References:  40
β-Lactamase reporter assay
Species:  Human
Tissue:  HEK293/Cre-bla cells
Response measured:  Elevated β-lactamase activity
References:  23
Measurement of cAMP levels in HEK293 cells transfected with the rat TA1 receptor.
Species:  Rat
Tissue:  HEK293 cells
Response measured:  Intracellular cAMP accumulation
References:  60
Mobilization of internal calcium in RD-HGA16cells transfected with unmodified human TA1
Species:  Human
Tissue:  RD-HGA16 cells
Response measured:  Mobilization of intracellular calcium
References:  27-28
Inhibition of firing frequency of dopamine neurones in slice preparation of mouse brain ventral tegmental area.
Species:  Mouse
Tissue:  Midbrain slice
Response measured:  Inhibition of spontaneous dopamine neurone firing frequency
References:  7
β-Lactamase reporter assay
Species:  Mouse
Tissue:  HEK293/Cre-bla cells
Response measured:  Elevated β-lactamase activity
References:  23
Activation of leukocytes
Species:  Human
Tissue:  PMN, T and B cells
Response measured:  Chemotactic migration towards TA1 ligands (β-Phenylethylamine, tyramine and 3-iodothyronamine), trace amine induced IL-4 secretion (T-cells) and trace amine induced regulation of T cell marker RNA expression, trace amine induced IgE secretion in B cells.
References:  4
Measurement of cAMP levels in human cultured astrocytes.
Species:  Human
Tissue:  Astrocytes
Response measured:  cAMP accumulation
References:  10
Increase in glucose-dependent insulin secretion
Species:  Rat
Tissue:  INS1E cells
Response measured:  Potentiation of glucose-induced insulin secretion
References:  45
Functional Assay Comments
Expression systems have proved effective in establishing assays for TA1 activity without the need for specific agonists and antagonists.
Physiological Functions Click here for help
β-PEA inhibited uptake and induced efflux of [3H]dopamine and [3H]serotonin in striatal and [3H]norepinephrine in thalamic synaptosomes of wild-type mice and in HEK293 cells expressing TA1.
Species:  Mouse
Tissue:  Striatal and thalamic synaptosomes.
References:  64,67
Inhibition of firing frequency of dopminergic neurones
Species:  Mouse
Tissue:  Brain
References:  7,30,49-50
RO5166017 and RO5263397 inhibited expression of cocaine memory. Repeated administration of RO5166017 showed continually inhibitory effect on expression of cocaine reward memory but no no effect on reconsolidation, extinction, or storage of cocaine reward memory.
Species:  Rat
Tissue:  in vivo whole animal
References:  33
Improvement in glucose tolerance following an oral glucose tolerance test and reduction in body weight in wild type and diabetic db/db mice in response to TAAR1 agonist RO5166017.
Species:  Mouse
Tissue:  in vivo whole animal
References:  45
The selectve Taar1 agonists RO5203648 (partial agonist) and RO5256390 (full agonist) reduced reinforcing and rewarding properties of cocaine.
Species:  Rat
Tissue:  in vivo whole animal
References:  43
Physiological Consequences of Altering Gene Expression Click here for help
Mice deficient in the TA1 receptor possess a phenotype with minor spontaneous hyperactivity, reduced prepulse inhibition, increased sensitisation to the psychomotor-stimulating effects of amphetamine, raised levels of dopamine and noradrenaline in the dorsal striatum, increased striatal D2 receptor expression and an elevated spontaneous firing rate of dopaminergic neurons in the ventral tegmental area compared with the wild type. This has been proposed as an animal model of schizophrenia and also as hemi-parkinsonian.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  30,55,63
β-PEA inhibited uptake and induced efflux of [3H]dopamine and [3H]serotonin in striatal and [3H]norepinephrine in thalamic synaptosomes of wild-type but not TA1 knockout mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  64,67
Knockout animals exhibit a significant augmentation of methamphetamine induced locomotor activity and conditioned placement preference.
Species:  Mouse
Tissue:  in vivo whole animal
Technique:  Targeting in embryonic stem cells
References:  1
Functional interaction between TA1 and Dopamine D2 receptor. In TA1 knockout mouse haloperidol -induced striatal c-Fos expression and catalepsy are reduced.
Species:  Mouse
Tissue:  in vivo whole animal
Technique:  Targeting in embryonic stem cells
References:  16
Auto-inhibition of MDMA (Ecstasy) responses by TA1 receptor. Knockout animals indicate a role for TA1 in MDMA mediated hypothermia and in auto-inhibition of MDMA responses including release of dopamine and 5-HT in dorsal striatum and nucleus accumbens, locomotor activity, striatal tyrosine hydrolxylase phsophorylation.
Species:  Mouse
Tissue:  in vivo whole animal
Technique:  Targeting in embryonic stem cells
References:  13
Brain-specific overexpression of TA1 alters monoaminergic neurotransmission and decreased sensitivty to amphetamine. Increased spontaneous firing activity of monaminergic neurones in ventral tegmental area, dorsal raphe nucleus and locus coeruleus resulting from reduced GABAergic inhibitory input. Elevated basal release of monoamines. Hyposensitivity to locomotor effects of amphetamine that could be reversed with the TA1 partial agonist RO5073012.
Species:  Mouse
Tissue:  in vivo whole animal
Technique:  Gene over expression
References:  48
Basal and stimulated dopamine (DA) release was higher in the nucleus accumbens of TA1-KO mice in vivo and ex vivo but DAT function remained unaltered. The TA1 agonist RO5166017 had no effect on DA release from the nucleus accumbens in brain slices from TA1-KO mice but decreased evoked DA release in tissue from WT animals that was prevented by the TA1 antagonist EPPTB. The D2 agonist quinpirole decreased DA release in both WT and KO brain slices and this decrease was augmented in the presence of RO5166017 in the WT but not KO tissues, suggesting close interaction between TA1 and D2 autoreceptor regulation of dopamine release in the mouse nucleus accumbens that was confirmed by a paired pulse experiment.
Species:  Mouse
Tissue:  in vivo whole animal and in vitro brain slices
Technique:  Targeting in embryonic stem cells
References:  26
TA1 KO mice showed greater preference for/consumption of ethanol, more sedation and less locomotor activity in response to acute ethanol than wild type animals.
Species:  Mouse
Tissue:  in vivo whole animal
Technique:  Gene targeting in embryonic stem cells
References:  35
Climbing and some stereotypies elicited by high dose apomorphine (2-5mg kg-1) were decreased in the TA1 KO mouse compared to wild type.
Species:  Mouse
Tissue:  in vivo whole animal
Technique:  Gene targeting in embryonic stem cells
References:  57
Mice deficient in TA1 receptor lack the the glucose lowering and food consumption reduction response to RO5166017 observed in wild type animals.
Species:  Mouse
Tissue:  in vivo whole animal
Technique:  Gene targeting in embryonic stem cells
References:  45
TA1 knockout mice exhibited less severe dopaminergic neurodegeneration following intrastriatal administration of 6-hydroxydopamine than wild type controls. Following medial forebrain bundle administration of 6-hydroxydopamine and subsequent L-DOPA treatment, TA1 KO mice exhibited more pronounced rotational behaviour and dyskinesia but this could be counteracted by RO5166017.
Species:  Mouse
Tissue:  in vivo whole animal and brain
Technique:  Gene targeting in embryonic stem cells
References:  3
D2, but not D1, dopamine receptors were over-expressed at mRNA and protein levels, in the striatum of TA1 KO mice and exhibited pronounced supersensitivity.
Species:  Mouse
Tissue:  in vivo whole animal and striatum
Technique:  Gene targeting in embryonic stem cells
References:  14
TA1 KO mice show altered subunit composition and reduced functionality of NMDA receptors resulting in dysregulated cortical glutaminergic transmission and aberrant behavoiurs consistent with a perseverative and impulsive phenotype.
Species:  None
Tissue:  in vivo whole animal and brain
Technique:  Gene targeting in embryonic stem cells
References:  15
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Taar1tm1Tdw Taar1tm1Tdw/Taar1tm1Tdw
involves: 129S1/Sv * C57BL/6J		 MGI:2148258  MP:0003964 abnormal noradrenaline level PMID: 17212650 
Taar1tm1Tdw Taar1tm1Tdw/Taar1tm1Tdw
involves: 129S1/Sv * C57BL/6J		 MGI:2148258  MP:0003088 abnormal prepulse inhibition PMID: 17212650 
Taar1tm1Tdw Taar1tm1Tdw/Taar1tm1Tdw
involves: 129S1/Sv * C57BL/6J		 MGI:2148258  MP:0009749 enhanced behavioral response to addictive substance PMID: 17212650 
Taar1tm1Tdw Taar1tm1Tdw/Taar1tm1Tdw
involves: 129S1/Sv * C57BL/6J		 MGI:2148258  MP:0001906 increased dopamine level PMID: 17212650 
Taar1tm1Tdw Taar1tm1Tdw/Taar1tm1Tdw
involves: 129S1/Sv * C57BL/6J		 MGI:2148258  MP:0008873 increased physiological sensitivity to xenobiotic PMID: 17212650 
Biologically Significant Variant Comments
A SNP (rs8192619) in the TA1 receptor was reported in a large candidate gene association study investigating genetic risk factors that may contribute to the aetiology of fibromyalgia [53].
General Comments
For comprehensive reviews of the TA1 receptor see: [25,36-37,42,44,54,65].

References

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1. Achat-Mendes C, Lynch LJ, Sullivan KA, Vallender EJ, Miller GM. (2012) Augmentation of methamphetamine-induced behaviors in transgenic mice lacking the trace amine-associated receptor 1. Pharmacol Biochem Behav, 101 (2): 201-7. [PMID:22079347]

2. Adriaenssens A, Lam BY, Billing L, Skeffington K, Sewing S, Reimann F, Gribble F. (2015) A Transcriptome-Led Exploration of Molecular Mechanisms Regulating Somatostatin-Producing D-Cells in the Gastric Epithelium. Endocrinology, 156 (11): 3924-36. [PMID:26241122]

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