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Gene Review

EGR1  -  early growth response 1

Gallus gallus

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Disease relevance of EGR1

  • Relative Axial Myopia in Egr-1 (ZENK) Knockout Mice [1].
  • Defocus produced significant changes in ZENK expression only in the case of 4D of imposed hyperopia, but these changes were in the opposite direction to what was previously observed in vivo [2].

High impact information on EGR1

  • We identified candidate regulatory neurons by immunocytochemistry for immediate-early gene products, ZENK (zif268, Egr-1) and Fos, after appropriate visual stimulation [3].
  • ZENK synthesis was enhanced by conditions that suppress ocular elongation (plus defocus, termination of form deprivation) and suppressed by conditions that enhance ocular elongation (minus defocus, form deprivation), particularly in glucagon-containing amacrine cells [3].
  • We further demonstrate that there are regions in the 3' untranslated area of the ZENK gene that are as highly conserved as the protein-coding region and that may play a role in postranscriptional regulatory mechanisms of ZENK gene expression [4].
  • We have previously shown that a cloned 480 bp DNA fragment that spans the 3'-enhancer region of the avian beta-globin gene cluster can become very tightly, perhaps covalently, bound to protein in avian nuclear matrices in vitro [Zenk et al. (1990) Biochemistry 29, 5221-5226] [5].
  • Because of this pattern of gene expression, we have compared the level of the ZENK mRNA in chicks that have been subjected to a 30-min acoustic imprinting paradigm and in untrained controls [6].

Chemical compound and disease context of EGR1

  • We have tested whether the muscarinic antagonists atropine, pirenzepine, oxyphenonium, gallamine, MT-3, himbacine, and 4-DAMP can stimulate ZENK expression so that the drugs' inhibitory effect on myopia development could be explained by an enhanced STOP signal [7].

Biological context of EGR1


Anatomical context of EGR1

  • Our results reveal a significant increase (P< or =0.05) in the level of the ZENK mRNA in MNH and Field L, and in the two forebrain hemispheres; no increase was seen in the ectostriatum, which is a visual projection area [6].
  • The chicken immediate-early gene ZENK is expressed in the medio-rostral neostriatum/hyperstriatum ventrale, a brain region involved in acoustic imprinting, and is up-regulated after exposure to an auditory stimulus [6].
  • CONCLUSIONS: Imposed defocus triggers extensive transcriptional changes of ZENK in the retina, and of TGFbeta-2 and RALHD-2 in the choroid [8].

Associations of EGR1 with chemical compounds

  • Because it is known that intravitreal quisqualic acid (QA) eliminates most cholinergic neurons in the retina within 6 or 7 days, in a second set of experiments, we tested whether these antagonists could still stimulate ZENK production, 6 days after QA was applied [7].
  • The RA system differs from a number of other candidates (dopamine, cholinergic agents, opiates) in that it distinguishes between positive and negative defocus, similar to the immediate early gene ZENK (Stell et al., 1999) [9].
  • We have measured early changes in mRNA levels, in response to imposed negative and positive defocus, of the transcription factor ZENK, the retinoic acid synthesis enzyme RALDH-2, and the growth factor TGFbeta-2 [8].

Analytical, diagnostic and therapeutic context of EGR1


  1. Relative Axial Myopia in Egr-1 (ZENK) Knockout Mice. Schippert, R., Burkhardt, E., Feldkaemper, M., Schaeffel, F. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  2. ZENK expression of retinal glucagon amacrine cells in chicks: the effect of defocus presented in vivo, in vitro and under anesthesia. Bitzer, M., Schaeffel, F. Vision Res. (2006) [Pubmed]
  3. Light- and focus-dependent expression of the transcription factor ZENK in the chick retina. Fischer, A.J., McGuire, J.J., Schaeffel, F., Stell, W.K. Nat. Neurosci. (1999) [Pubmed]
  4. Evolutionary conservation of the immediate-early gene ZENK. Long, K.D., Salbaum, J.M. Mol. Biol. Evol. (1998) [Pubmed]
  5. Avian nuclear matrix proteins bind very tightly to cellular DNA of the beta-globin gene enhancer in a tissue-specific fashion. Brotherton, T., Zenk, D., Kahanic, S., Reneker, J. Biochemistry (1991) [Pubmed]
  6. The chicken immediate-early gene ZENK is expressed in the medio-rostral neostriatum/hyperstriatum ventrale, a brain region involved in acoustic imprinting, and is up-regulated after exposure to an auditory stimulus. Thode, C., Bock, J., Braun, K., Darlison, M.G. Neuroscience (2005) [Pubmed]
  7. Effects of muscarinic antagonists on ZENK expression in the chicken retina. Bitzer, M., Kovacs, B., Feldkaemper, M., Schaeffel, F. Exp. Eye Res. (2006) [Pubmed]
  8. Early transcriptional changes of retinal and choroidal TGFbeta-2, RALDH-2, and ZENK following imposed positive and negative defocus in chickens. Simon, P., Feldkaemper, M., Bitzer, M., Ohngemach, S., Schaeffel, F. Mol. Vis. (2004) [Pubmed]
  9. Visually induced changes in components of the retinoic acid system in fundal layers of the chick. Bitzer, M., Feldkaemper, M., Schaeffel, F. Exp. Eye Res. (2000) [Pubmed]
  10. Effects of quisqualic acid on retinal ZENK expression induced by imposed defocus in the chick eye. Bitzer, M., Schaeffel, F. Optometry and vision science : official publication of the American Academy of Optometry. (2004) [Pubmed]
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