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nicotinic acetylcholine receptor β4 subunit

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Target not currently curated in GtoImmuPdb

Target id: 474

Nomenclature: nicotinic acetylcholine receptor β4 subunit

Family: Nicotinic acetylcholine receptors (nACh)

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 498 15q25.1 CHRNB4 cholinergic receptor nicotinic beta 4 subunit 7
Mouse 4 495 9 B Chrnb4 cholinergic receptor, nicotinic, beta polypeptide 4 3
Rat 4 495 8q24 Chrnb4 cholinergic receptor nicotinic beta 4 subunit 2
Previous and Unofficial Names Click here for help
Acrb4 | cholinergic receptor, nicotinic, beta 4 (neuronal) | cholinergic receptor, nicotinic beta 4 | cholinergic receptor
Database Links Click here for help
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Natural/Endogenous Ligands Click here for help
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cellular signalling
Tissue Distribution Click here for help
Brain: medial habenula, mitral cell layer and the accessory olfactory bulb, interpeduncular nucleus, inferior colliculus and the medial vestibular nucleus (mRNA restricted to relatively few nuclei).
Expression level:  High
Species:  Mouse
Technique:  Radioligand binding
References:  13
Brain: medial habenula, cerebral cortex, hippocampus, motor trigeminal nucleus, locus coreulus, cerebellum, interpeduncular nucleus (no expression in thalamus).
Expression level:  High
Species:  Rat
Technique:  in situ hybridisation
References:  2
Tissue Distribution Comments
Deletion of β4 subunit in knockout mice has little effect on total [3H]- or [125I]-epibatidine binding with the exception of a partial reduction in the signal intensity in the fasiculus retroflexus, interpeduncular nucleus and the inferior colliculus. The effects of β4 gene deletion were more readily observable when cytisine was included in the incubation with [3H]- or [125I]-epibatidine. Under these experimental conditions, robust effects could be observed in the medial habenula, the fasiculus retroflexis, the interpeducular nucleus and the inferior colliculus, all of which expressed high levels of cytisine-resistant [125I]epibatidine binding [1,10].

Expression of β4 mRNA in rhesus monkey (Macaca mulatta) brain is similar to that described in rodents. High expression is detected in thalamic nuclei, substantia nigra pars compacta and vertral tegmental area. Expression is also detected in cortex (layer VI showing the highest level of expression) and lower levles in hippocampus and caudate [4].

Expression of β4 mRNA in suirrel monkey (Samimiri sciureus) appears to differ from that in rodents or macaques. High levels of expression brain have been detected in caudate, putamen and hippocampus. However, compared to expression levels in the cotex, levels of expression were relatively low in thalamic nuclei, substantia nigra pars compacta and medial habenula [6].
Physiological Consequences of Altering Gene Expression Click here for help
Knockout mice display reduced acetylcholine-activated whole-cell currents in superior cervical ganglion neurons; autonomic cardiac and intestinal dysfunction are also observed; decreased anxiety-related responses; resistance to nicotine-induced seizures; decreased nicotine withdrawal. Expression of α3 subunit mRNA is greatly reduced in the mitral cell layer of the olfactory bulb, and the inferior and the superior colliculus of β4 knockout mice.
Species:  Mouse
Tissue:  in vivo
Technique:  Gene knockout
References:  5,9,11-12,14
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Sporadic amyotrophic lateral sclerosis
Synonyms: SALS
Disease Ontology: DOID:332
OMIM: 105400
References:  8
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R136W 8
Missense Human R136Q 8
Missense Human R349C 1045C>T 8


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1. Baddick CG, Marks MJ. (2011) An auroradiographic survey of mouse brain nicotinic acetylcholine receptors defined by null mutants. Biochem Pharmacol,,. [PMID:21575611]

2. Duvoisin RM, Deneris ES, Patrick J, Heinemann S. (1989) The functional diversity of the neuronal nicotinic acetylcholine receptors is increased by a novel subunit: beta 4. Neuron, 3 (4): 487-96. [PMID:2642007]

3. Eng CM, Kozak CA, Beaudet AL, Zoghbi HY. (1991) Mapping of multiple subunits of the neuronal nicotinic acetylcholine receptor to chromosome 15 in man and chromosome 9 in mouse. Genomics, 9 (2): 278-82. [PMID:2004777]

4. Han ZY, Le Novère N, Zoli M, Hill JA, Champtiaux N, Changeux JP. (2000) Localization of nAChR subunit mRNAs in the brain of Macaca mulatta. Eur J Neurosci, 12 (10): 3664-74. [PMID:11029636]

5. Kedmi M, Beaudet AL, Orr-Urtreger A. (2004) Mice lacking neuronal nicotinic acetylcholine receptor beta4-subunit and mice lacking both alpha5- and beta4-subunits are highly resistant to nicotine-induced seizures. Physiol Genomics, 17 (2): 221-9. [PMID:14996991]

6. Quik M, Polonskaya Y, Gillespie A, Jakowec M, Lloyd GK, Langston JW. (2000) Localization of nicotinic receptor subunit mRNAs in monkey brain by in situ hybridization. J Comp Neurol, 425 (1): 58-69. [PMID:10940942]

7. Raimondi E, Rubboli F, Moralli D, Chini B, Fornasari D, Tarroni P, De Carli L, Clementi F. (1992) Chromosomal localization and physical linkage of the genes encoding the human alpha 3, alpha 5, and beta 4 neuronal nicotinic receptor subunits. Genomics, 12 (4): 849-50. [PMID:1572664]

8. Sabatelli M, Eusebi F, Al-Chalabi A, Conte A, Madia F, Luigetti M, Mancuso I, Limatola C, Trettel F, Sobrero F et al.. (2009) Rare missense variants of neuronal nicotinic acetylcholine receptor altering receptor function are associated with sporadic amyotrophic lateral sclerosis. Hum Mol Genet, 18 (20): 3997-4006. [PMID:19628475]

9. Salas R, Cook KD, Bassetto L, De Biasi M. (2004) The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice. Neuropharmacology, 47 (3): 401-7. [PMID:15275829]

10. Salas R, Pieri F, De Biasi M. (2004) Decreased signs of nicotine withdrawal in mice null for the beta4 nicotinic acetylcholine receptor subunit. J Neurosci, 24 (45): 10035-9. [PMID:15537871]

11. Salas R, Pieri F, Fung B, Dani JA, De Biasi M. (2003) Altered anxiety-related responses in mutant mice lacking the beta4 subunit of the nicotinic receptor. J Neurosci, 23 (15): 6255-63. [PMID:12867510]

12. Wang N, Orr-Urtreger A, Chapman J, Rabinowitz R, Korczyn AD. (2003) Deficiency of nicotinic acetylcholine receptor beta 4 subunit causes autonomic cardiac and intestinal dysfunction. Mol Pharmacol, 63 (3): 574-80. [PMID:12606764]

13. Whiteaker P, Jimenez M, McIntosh JM, Collins AC, Marks MJ. (2000) Identification of a novel nicotinic binding site in mouse brain using [(125)I]-epibatidine. Br J Pharmacol, 131 (4): 729-39. [PMID:11030722]

14. Xu C, Lu Y, Tang G, Wang R. (1999) Expression of voltage-dependent K(+) channel genes in mesenteric artery smooth muscle cells. Am J Physiol, 277 (5): G1055-63. [PMID:10564112]


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