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Gene Review

Penk  -  preproenkephalin

Mus musculus

Synonyms: AI326464, ENK, PPA, Penk1, Proenkephalin-A
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Disease relevance of Penk1


Psychiatry related information on Penk1


High impact information on Penk1

  • Other induced T-helper cell lines have 0.1 to 0.5 percent of their mRNA as preproenkephalin mRNA [8].
  • A complementary DNA (cDNA) library prepared from a cloned concanavalin A-activated mouse T-helper cell line was screened for abundant and induction-specific cDNA's. One such randomly chosen cDNA was found to encode mouse preproenkephalin messenger RNA (mRNA) [8].
  • To assess the role that these cis-acting elements could play in preproenkephalin expression and regulation in vivo, the expression of a construct containing this 200-base-pair region fused to the chloramphenicol acetyltransferase gene was examined in transgenic mice [9].
  • These elements confer trans-synaptic regulation in two well-studied models of trans-synaptic preproenkephalin upregulation but not in a third system, underscoring the specificity of the regulatory sequence elements implicated in the synaptic regulation of neuronal genes [9].
  • Apparent full-length cDNAs containing the sequences of 14 of the 16 initial isolates were sequenced and were found to represent five different species of mRNA; three of the five species were identical to previously reported cDNA sequences of preproenkephalin, T-cell-replacing factor, and a serine esterase, respectively [10].

Chemical compound and disease context of Penk1


Biological context of Penk1

  • RESULTS: Penk1(-/-) mice showed exaggerated responses to painful or threatening environmental stimuli, but the expressivity of the mutant phenotype was strongly dependent on the behavioral paradigm and on the genetic background [5].
  • CONCLUSIONS: (1) The behavioral effects of the Penk1 gene deletion persists on different genetic backgrounds, but its detection sometimes requires the use of different behavioral paradigms [5].
  • MOR -/- mice are useful models for studying cocaine effects on ppEnk gene expression that could aid interpretation of the similar postmortem phenomena found in human cocaine addicts [12].
  • The positional and sequence homologies between the rat and the mouse ENK genes decrease in more upstream regions due to the presence of nonhomologues repetititve DNA sequences [13].
  • Several cis-regulatory DNA elements are present in the 5' upstream regulatory region of the enkephalin gene (ENK) promoter [14].

Anatomical context of Penk1


Associations of Penk1 with chemical compounds


Regulatory relationships of Penk1


Other interactions of Penk1

  • Impaired preprodynorphin, but not preproenkephalin, mRNA induction in the striatum of mGluR1 mutant mice in response to acute administration of the full dopamine D(1) agonist SKF-82958 [23].
  • In addition, we found that the DOR-1 and ppENK knock-outs as well as the NMDA receptor-deficient 129S6 inbred mouse strain, which also lacks tolerance, exhibit antagonist-induced opioid withdrawal [24].
  • Role of mu -opioid receptor in modulation of preproenkephalin mRNA expression and opioid and dopamine receptor binding in methamphetamine-sensitized mice [17].
  • This is the first evidence of a SOM/ENK projection from the ventral medulla to either the spinal cord or NTS [19].
  • Interestingly, terminals containing DOR-1-ir appeared to be closely apposed by fibers and terminals containing enkephalin (ENK)-ir, which suggests that ENK may be a physiologically relevant ligand for the receptor encoded by DOR-1, and that DOR-1 may act to regulate the release of transmitters from small diameter primary afferent neurons [25].

Analytical, diagnostic and therapeutic context of Penk1


  1. Th2-dependent airway eosinophilia is regulated by preproenkephalin. Hook, S., Prout, M., Camberis, M., Konig, M., Zimmer, A., Van Heeke, G., Le Gros, G. J. Neuroimmunol. (2000) [Pubmed]
  2. Antihyperalgesic effects of infection with a preproenkephalin-encoding herpes virus. Wilson, S.P., Yeomans, D.C., Bender, M.A., Lu, Y., Goins, W.F., Glorioso, J.C. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  3. Critical role of preproenkephalin in experimental autoimmune encephalomyelitis. Weir, C., McNeill, A., Hook, S., Harvie, M., La Flamme, A.C., Le Gros, G., B??ckstr??m, B.T. J. Neuroimmunol. (2006) [Pubmed]
  4. Preproenkephalin mRNA in T-cells, macrophages, and mast cells. Martin, J., Prystowsky, M.B., Angeletti, R.H. J. Neurosci. Res. (1987) [Pubmed]
  5. Behavioral phenotype of pre-proenkephalin-deficient mice on diverse congenic backgrounds. Bilkei-Gorzo, A., Racz, I., Michel, K., Zimmer, A., Klingmüller, D., Zimmer, A. Psychopharmacology (Berl.) (2004) [Pubmed]
  6. Differential changes in striatal projection neurons in R6/2 transgenic mice for Huntington's disease. Sun, Z., Del Mar, N., Meade, C., Goldowitz, D., Reiner, A. Neurobiol. Dis. (2002) [Pubmed]
  7. Recovery and measurement of specific RNA species from postmortem brain tissue: a general reduction in Alzheimer's disease detected by molecular hybridization. Taylor, G.R., Carter, G.I., Crow, T.J., Johnson, J.A., Fairbairn, A.F., Perry, E.K., Perry, R.H. Exp. Mol. Pathol. (1986) [Pubmed]
  8. Activation of mouse T-helper cells induces abundant preproenkephalin mRNA synthesis. Zurawski, G., Benedik, M., Kamb, B.J., Abrams, J.S., Zurawski, S.M., Lee, F.D. Science (1986) [Pubmed]
  9. Preproenkephalin promoter "cassette" confers brain expression and synaptic regulation in transgenic mice. Donovan, D.M., Takemura, M., O'Hara, B.F., Brannock, M.T., Uhl, G.R. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  10. cDNA sequences of two inducible T-cell genes. Kwon, B.S., Weissman, S.M. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  11. Expression of the preproenkephalin A gene in tumor cells and brain glioma: a northern and in situ hybridization study. Rost, N., Chaffanet, M., Nissou, M.F., Chauvin, C., Foote, A.M., Lainé, M., Benabid, A.L. Neuropeptides (1989) [Pubmed]
  12. Effects of acute "binge" cocaine on preprodynorphin, preproenkephalin, proopiomelanocortin, and corticotropin-releasing hormone receptor mRNA levels in the striatum and hypothalamic-pituitary-adrenal axis of mu-opioid receptor knockout mice. Zhou, Y., Spangler, R., Schlussman, S.D., Yuferov, V.P., Sora, I., Ho, A., Uhl, G.R., Kreek, M.J. Synapse (2002) [Pubmed]
  13. Isolation and structural and genetic analysis of the mouse enkephalin gene and its d(AC/TG)n repeats. v Agoston, D., Santha, E., Shieh, G., Lala, R., Dobi, A. DNA Seq. (1998) [Pubmed]
  14. Far-upstream elements are dispensable for tissue-specific proenkephalin expression using a Cre-mediated knock-in strategy. Le, Y., Gagneten, S., Larson, T., Santha, E., Dobi, A., v Agoston, D., Sauer, B. J. Neurochem. (2003) [Pubmed]
  15. Opioidergic and dopaminergic gene expression in the caudate-putamen and accumbens of the mutant mouse, tottering (tg/tg). De Bartolomeis, A., Koprivica, V., Pickar, D., Crawley, J.N., Abbott, L.C. Brain Res. Mol. Brain Res. (1997) [Pubmed]
  16. Absence of preproenkephalin increases the threshold for T cell activation. Hook, S., Camberis, M., Prout, M., Le Gros, G. J. Neuroimmunol. (2003) [Pubmed]
  17. Role of mu -opioid receptor in modulation of preproenkephalin mRNA expression and opioid and dopamine receptor binding in methamphetamine-sensitized mice. Tien, L.T., Ho, I.K., Loh, H.H., Ma, T. J. Neurosci. Res. (2007) [Pubmed]
  18. Ventral striatopallidal oxytocin and vasopressin V1a receptors in the monogamous prairie vole (Microtus ochrogaster). Lim, M.M., Murphy, A.Z., Young, L.J. J. Comp. Neurol. (2004) [Pubmed]
  19. Neurons of the ventral medulla oblongata that contain both somatostatin and enkephalin immunoreactivities project to nucleus tractus solitarii and spinal cord. Millhorn, D.E., Seroogy, K., Hökfelt, T., Schmued, L.C., Terenius, L., Buchan, A., Brown, J.C. Brain Res. (1987) [Pubmed]
  20. Nicotine-induced antinociception, rewarding effects, and physical dependence are decreased in mice lacking the preproenkephalin gene. Berrendero, F., Mendizábal, V., Robledo, P., Galeote, L., Bilkei-Gorzo, A., Zimmer, A., Maldonado, R. J. Neurosci. (2005) [Pubmed]
  21. Preproenkephalin knockout mice show no depression-related phenotype. Bilkei-Gorzo, A., Michel, K., Noble, F., Roques, B.P., Zimmer, A. Neuropsychopharmacology (2007) [Pubmed]
  22. Differential regulation of the dopamine D1, D2 and D3 receptor gene expression and changes in the phenotype of the striatal neurons in mice lacking the dopamine transporter. Fauchey, V., Jaber, M., Caron, M.G., Bloch, B., Le Moine, C. Eur. J. Neurosci. (2000) [Pubmed]
  23. Impaired preprodynorphin, but not preproenkephalin, mRNA induction in the striatum of mGluR1 mutant mice in response to acute administration of the full dopamine D(1) agonist SKF-82958. Mao, L., Conquet, F., Wang, J.Q. Synapse (2002) [Pubmed]
  24. Genetic dissociation of opiate tolerance and physical dependence in delta-opioid receptor-1 and preproenkephalin knock-out mice. Nitsche, J.F., Schuller, A.G., King, M.A., Zengh, M., Pasternak, G.W., Pintar, J.E. J. Neurosci. (2002) [Pubmed]
  25. Immunofluorescent identification of a delta (delta)-opioid receptor on primary afferent nerve terminals. Dado, R.J., Law, P.Y., Loh, H.H., Elde, R. Neuroreport (1993) [Pubmed]
  26. Tolerance develops in spinal cord, but not in brain with chronic [Dmt1]DALDA treatment. Ben, Y., Smith, A.P., Schiller, P.W., Lee, N.M. Br. J. Pharmacol. (2004) [Pubmed]
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