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Gene Review

Chrna7  -  cholinergic receptor, nicotinic, alpha...

Mus musculus

Synonyms: Acra7, Neuronal acetylcholine receptor subunit alpha-7, alpha7, alpha7 nicotinic receptor, alpha7-nAChR
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Disease relevance of Chrna7


Psychiatry related information on Chrna7


High impact information on Chrna7


Chemical compound and disease context of Chrna7

  • Administration of nicotine, an alpha7 agonist that mimics vagus nerve stimulation, increases proinflammatory cytokine production and lethality from polymicrobial sepsis in splenectomized mice, indicating that the spleen is critical to the protective response of the cholinergic pathway [13].
  • In vivo, methyllycaconitine (MLA), a specific alpha-7 nAChR antagonist, significantly prevented MDMA-induced neurotoxicity at dopaminergic but not at serotonergic level, without affecting MDMA-induced hyperthermia [14].

Biological context of Chrna7

  • Mice engineered with a double-null disruption of the Chrna7 gene displayed only faint fluorescence on the midpiece, suggesting that the CHRNA7 contributed the majority of the observed alpha-bungarotoxin binding sites [15].
  • The mapping of a putative Chrna7 neuronal enhancer inside the deletion has significant implications for understanding the transcriptional regulation of this schizophrenia-susceptibility candidate gene [16].
  • The mouse alpha 7 subunit gene encodes a protein of 502 amino acids with substantial identity to the rat (99.6%), human (92.8%), and chicken (87.5%) amino acid sequences [17].
  • Targeted deletion of the kynurenine aminotransferase ii gene reveals a critical role of endogenous kynurenic acid in the regulation of synaptic transmission via alpha7 nicotinic receptors in the hippocampus [6].
  • The data suggest that hippocampal alpha7 receptor development is controlled predominantly by a region of mouse chromosome 7 that contains the strain-specific Chrna7 allele [18].

Anatomical context of Chrna7

  • Sperm from Chrna7(-/-) mice display no difference in number, morphology, viability or spontaneous acrosome reaction rate compared with Chrna7(+/+) sperm [15].
  • We confirm by reverse-transcription-polymerase chain reaction the expression in adult mouse testis of Chrna7 mRNA and demonstrate the subunit's presence in mouse sperm by immunoblot [15].
  • The Chrna7 results are explained by hypothesizing loss of an essential neuronal transcriptional enhancer required for approximately 80% of allelic Chrna7 promoter activity, while the Chrna7 promoter is upregulated in B lymphocytes by the transgene immunoglobulin enhancer [16].
  • An age-related increase in the (125)I-alphabungarotoxin ((125)I-alphaBTX) binding (specific to alpha7 nAChRs) was observed in the adrenal medulla of 3, 7 and 10 months old control mice [19].
  • In 21-d-old mKat-2-/- mice, endogenous alpha7* nAChR activity in the hippocampus was also increased, leading to an enhancement of GABAergic activity impinging onto CA1 pyramidal neurons that could be reduced significantly by acute exposure to KYNA (100 nM) [6].

Associations of Chrna7 with chemical compounds

  • Whereas in wild-type mice nicotine induced a persistent increase of synaptic efficacy via alpha7 nicotine acetylcholine receptors, in AD11 mice this alkaloid failed to modify synaptic strength [20].
  • Cloning and mapping of the mouse alpha 7-neuronal nicotinic acetylcholine receptor [17].
  • The nicotinergic chemotaxis of keratinocytes was most pronounced towards the concentration gradient of choline, a potent agonist of alpha7 nicotinic acetylcholine receptor [2].
  • The depolarization component that is resistant to alphaCTxGI was antagonized by pancuronium (3-10 microM) and by a 4-oxystilbene derivative (F3, 0.1-0.5 microM) at concentrations considered highly specific for alpha7* nAChRs [21].
  • A threonine for leucine 247 substitution in the channel domain of the chick alpha7 nAChR increases agonist affinity and decreases the rate of desensitization, creating a "gain of function" model for this receptor [22].

Physical interactions of Chrna7

  • One interaction of amyloid beta peptide that may contribute to an impairment of cognition is its high affinity binding to the alpha 7 nicotinic receptor; a receptor shown to be important for cognition in a number of studies [23].

Regulatory relationships of Chrna7

  • At this age, alpha7* nAChR activity induced by exogenous application of agonists to CA1 stratum radiatum interneurons was approximately 65% higher in mKat-2-/- than WT mice [6].
  • Knockout of the alpha7 nAChR gene selectively enhanced ethanol-induced neurotoxicity in a gene dosage-related fashion [4].

Other interactions of Chrna7


Analytical, diagnostic and therapeutic context of Chrna7


  1. The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in mice. van Westerloo, D.J., Giebelen, I.A., Florquin, S., Bruno, M.J., Larosa, G.J., Ulloa, L., Tracey, K.J., van der Poll, T. Gastroenterology (2006) [Pubmed]
  2. Differential regulation of keratinocyte chemokinesis and chemotaxis through distinct nicotinic receptor subtypes. Chernyavsky, A.I., Arredondo, J., Marubio, L.M., Grando, S.A. J. Cell. Sci. (2004) [Pubmed]
  3. Multiple calcium channels and kinases mediate alpha7 nicotinic receptor neuroprotection in PC12 cells. Ren, K., Puig, V., Papke, R.L., Itoh, Y., Hughes, J.A., Meyer, E.M. J. Neurochem. (2005) [Pubmed]
  4. alpha7 Nicotinic acetylcholine receptor knockout selectively enhances ethanol-, but not beta-amyloid-induced neurotoxicity. de Fiebre, N.C., de Fiebre, C.M. Neurosci. Lett. (2005) [Pubmed]
  5. Altered baroreflex responses in alpha7 deficient mice. Franceschini, D., Orr-Urtreger, A., Yu, W., Mackey, L.Y., Bond, R.A., Armstrong, D., Patrick, J.W., Beaudet, A.L., De Biasi, M. Behav. Brain Res. (2000) [Pubmed]
  6. Targeted deletion of the kynurenine aminotransferase ii gene reveals a critical role of endogenous kynurenic acid in the regulation of synaptic transmission via alpha7 nicotinic receptors in the hippocampus. Alkondon, M., Pereira, E.F., Yu, P., Arruda, E.Z., Almeida, L.E., Guidetti, P., Fawcett, W.P., Sapko, M.T., Randall, W.R., Schwarcz, R., Tagle, D.A., Albuquerque, E.X. J. Neurosci. (2004) [Pubmed]
  7. Deletion of the alpha7 nicotinic receptor subunit gene results in increased sensitivity to several behavioral effects produced by alcohol. Bowers, B.J., McClure-Begley, T.D., Keller, J.J., Paylor, R., Collins, A.C., Wehner, J.M. Alcohol. Clin. Exp. Res. (2005) [Pubmed]
  8. Impaired performance of alpha7 nicotinic receptor knockout mice in the five-choice serial reaction time task. Hoyle, E., Genn, R.F., Fernandes, C., Stolerman, I.P. Psychopharmacology (Berl.) (2006) [Pubmed]
  9. Tolerance to nicotine in mice lacking alpha7 nicotinic receptors. Naylor, C., Quarta, D., Fernandes, C., Stolerman, I.P. Psychopharmacology (Berl.) (2005) [Pubmed]
  10. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Wang, H., Liao, H., Ochani, M., Justiniani, M., Lin, X., Yang, L., Al-Abed, Y., Wang, H., Metz, C., Miller, E.J., Tracey, K.J., Ulloa, L. Nat. Med. (2004) [Pubmed]
  11. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Wang, H., Yu, M., Ochani, M., Amella, C.A., Tanovic, M., Susarla, S., Li, J.H., Wang, H., Yang, H., Ulloa, L., Al-Abed, Y., Czura, C.J., Tracey, K.J. Nature (2003) [Pubmed]
  12. Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. de Jonge, W.J., van der Zanden, E.P., The, F.O., Bijlsma, M.F., van Westerloo, D.J., Bennink, R.J., Berthoud, H.R., Uematsu, S., Akira, S., van den Wijngaard, R.M., Boeckxstaens, G.E. Nat. Immunol. (2005) [Pubmed]
  13. Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis. Huston, J.M., Ochani, M., Rosas-Ballina, M., Liao, H., Ochani, K., Pavlov, V.A., Gallowitsch-Puerta, M., Ashok, M., Czura, C.J., Foxwell, B., Tracey, K.J., Ulloa, L. J. Exp. Med. (2006) [Pubmed]
  14. Protection against MDMA-induced dopaminergic neurotoxicity in mice by methyllycaconitine: Involvement of nicotinic receptors. Chipana, C., Camarasa, J., Pubill, D., Escubedo, E. Neuropharmacology (2006) [Pubmed]
  15. Mice deficient in CHRNA7, a subunit of the nicotinic acetylcholine receptor, produce sperm with impaired motility. Bray, C., Son, J.H., Kumar, P., Meizel, S. Biol. Reprod. (2005) [Pubmed]
  16. Genetic mapping of putative Chrna7 and Luzp2 neuronal transcriptional enhancers due to impact of a transgene-insertion and 6.8 Mb deletion in a mouse model of Prader-Willi and Angelman syndromes. Stefan, M., Claiborn, K.C., Stasiek, E., Chai, J.H., Ohta, T., Longnecker, R., Greally, J.M., Nicholls, R.D. BMC Genomics (2005) [Pubmed]
  17. Cloning and mapping of the mouse alpha 7-neuronal nicotinic acetylcholine receptor. Orr-Urtreger, A., Seldin, M.F., Baldini, A., Beaudet, A.L. Genomics (1995) [Pubmed]
  18. Development of hippocampal alpha7 nicotinic receptors in C3H and DBA/2 congenic mice. Adams, C.E., Yonchek, J.C., Stitzel, J.A. Brain Res. (2006) [Pubmed]
  19. Expression of the alpha7, alpha4 and alpha3 nicotinic receptor subtype in the brain and adrenal medulla of transgenic mice carrying genes coding for human AChE and beta-amyloid. Mousavi, M., Nordberg, A. Int. J. Dev. Neurosci. (2006) [Pubmed]
  20. Failure of nicotine-dependent enhancement of synaptic efficacy at Schaffer-collateral CA1 synapses of AD11 anti-nerve growth factor transgenic mice. Sola, E., Capsoni, S., Rosato-Siri, M., Cattaneo, A., Cherubini, E. Eur. J. Neurosci. (2006) [Pubmed]
  21. Mouse muscle denervation increases expression of an alpha7 nicotinic receptor with unusual pharmacology. Tsuneki, H., Salas, R., Dani, J.A. J. Physiol. (Lond.) (2003) [Pubmed]
  22. Mice homozygous for the L250T mutation in the alpha7 nicotinic acetylcholine receptor show increased neuronal apoptosis and die within 1 day of birth. Orr-Urtreger, A., Broide, R.S., Kasten, M.R., Dang, H., Dani, J.A., Beaudet, A.L., Patrick, J.W. J. Neurochem. (2000) [Pubmed]
  23. Transgenic mice over-expressing human beta-amyloid have functional nicotinic alpha 7 receptors. Spencer, J.P., Weil, A., Hill, K., Hussain, I., Richardson, J.C., Cusdin, F.S., Chen, Y.H., Randall, A.D. Neuroscience (2006) [Pubmed]
  24. Cholinergic modulation of microglial activation by alpha 7 nicotinic receptors. Shytle, R.D., Mori, T., Townsend, K., Vendrame, M., Sun, N., Zeng, J., Ehrhart, J., Silver, A.A., Sanberg, P.R., Tan, J. J. Neurochem. (2004) [Pubmed]
  25. A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Impagnatiello, F., Guidotti, A.R., Pesold, C., Dwivedi, Y., Caruncho, H., Pisu, M.G., Uzunov, D.P., Smalheiser, N.R., Davis, J.M., Pandey, G.N., Pappas, G.D., Tueting, P., Sharma, R.P., Costa, E. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  26. Differential expression of alpha-bungarotoxin-sensitive neuronal nicotinic receptors in adrenergic chromaffin cells: a role for transcription factor Egr-1. Criado, M., Domínguez del Toro, E., Carrasco-Serrano, C., Smillie, F.I., Juíz, J.M., Viniegra, S., Ballesta, J.J. J. Neurosci. (1997) [Pubmed]
  27. Involvement of nicotinic acetylcholine receptors in suppression of antimicrobial activity and cytokine responses of alveolar macrophages to Legionella pneumophila infection by nicotine. Matsunaga, K., Klein, T.W., Friedman, H., Yamamoto, Y. J. Immunol. (2001) [Pubmed]
  28. Characterization of nicotinic acetylcholine receptors expressed in primary cultures of cerebellar granule cells. Didier, M., Berman, S.A., Lindstrom, J., Bursztajn, S. Brain Res. Mol. Brain Res. (1995) [Pubmed]
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