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Gene Review

Opn4  -  opsin 4 (melanopsin)

Mus musculus

Synonyms: 1110007J02Rik, Gm533, Melanopsin, Mop, Mopn, ...
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Disease relevance of Opn4


Psychiatry related information on Opn4


High impact information on Opn4


Biological context of Opn4

  • We have also generated mice lacking melanopsin coupled with disabled rod and cone phototransduction mechanisms [7].
  • The human melanopsin gene consists of 10 exons and is mapped to chromosome 10q22 [8].
  • This spectrum matches that for the pupillary light reflex in mice of the same genotype, and that for the intrinsic photosensitivity of the melanopsin-expressing retinal ganglion cells [7].
  • The unique inner retinal localization of melanopsin suggests that it is not involved in image formation but rather may mediate nonvisual photoreceptive tasks, such as the regulation of circadian rhythms and the acute suppression of pineal melatonin [8].
  • However, its amino-acid sequence differs from vertebrate photosensory opsins and some have suggested that melanopsin may be a photoisomerase, providing retinoid chromophore to an unidentified opsin [9].

Anatomical context of Opn4

  • In this study we provide the first clear evidence that Opn4 expression is not confined to these photosensitive RGCs, but is also expressed in the retinal pigment epithelium (RPE), a tissue with no known photosensensory role [10].
  • The discovery of melanopsin-dependent inner retinal photoreceptors in mammals has precipitated a fundamental reassessment of such non-image forming (NIF) light responses as circadian photoentrainment and the pupil light reflex [11].
  • Our results demonstrate for the first time a melanopsin-dependent regulation of visual processing within the retina, revealing an important function for inner retinal photoreceptors in optimizing classical visual pathways according to time of day [11].
  • To test this hypothesis, we have characterized melanopsin following heterologous expression in COS cells [1].
  • Opn4 mRNA is also regulated on a circadian basis in the pineal gland, reaching peak values of accumulation in the late subjective night [12].

Associations of Opn4 with chemical compounds


Regulatory relationships of Opn4

  • In summary, our experiments constitute the first direct demonstration that melanopsin forms a photopigment capable of activating a G-protein, but its spectral properties are not consistent with the action spectrum for circadian entrainment [1].
  • In these mice, the proportion of melanopsin RGCs that express Fos in response to light is significantly reduced [16].
  • In a reconstituted biochemical system, the reconstituted melanopsin was capable of activating transducin, the G-protein of rod photoreceptors, in a light-dependent manner [17].

Other interactions of Opn4

  • Genetic knockout studies revealed that functional melanopsin and rod-cone photoreceptive systems are required for the light-inducibility of PK2 [18].
  • Furthermore, melanopsin activated the photoreceptor G-protein, transducin, in a light-dependent manner [1].
  • We can preclude retinal contamination of RPE extracts as levels of Opn4 expression were higher in the RPE than in the retina, and the expression of rod opsin and Thy1 (a marker of the RGC layer) were barely detectable in RPE extracts [10].
  • Collectively, our data suggest that melanopsin RGCs form a heterogeneous population of neurons, and that most of the light-induced c-fos expression within these cells is associated with the endogenous photosensitivity of these neurons [16].
  • (2) Could the reported age-related decline in circadian photosensitivity of rodents be linked to changes in the population of melanopsin RGCs [16]?

Analytical, diagnostic and therapeutic context of Opn4


  1. Melanopsin forms a functional short-wavelength photopigment. Newman, L.A., Walker, M.T., Brown, R.L., Cronin, T.W., Robinson, P.R. Biochemistry (2003) [Pubmed]
  2. Analysis of the Vibrio pathogenicity island-encoded Mop protein suggests a pleiotropic role in the virulence of epidemic Vibrio cholerae. Zhang, D., Rajanna, C., Sun, W., Karaolis, D.K. FEMS Microbiol. Lett. (2003) [Pubmed]
  3. Melanopsin is required for non-image-forming photic responses in blind mice. Panda, S., Provencio, I., Tu, D.C., Pires, S.S., Rollag, M.D., Castrucci, A.M., Pletcher, M.T., Sato, T.K., Wiltshire, T., Andahazy, M., Kay, S.A., Van Gelder, R.N., Hogenesch, J.B. Science (2003) [Pubmed]
  4. Making (a) sense of non-visual ocular photoreception. Van Gelder, R.N. Trends Neurosci. (2003) [Pubmed]
  5. Nonvisual light responses in the Rpe65 knockout mouse: rod loss restores sensitivity to the melanopsin system. Doyle, S.E., Castrucci, A.M., McCall, M., Provencio, I., Menaker, M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. Inner retinal photoreception independent of the visual retinoid cycle. Tu, D.C., Owens, L.A., Anderson, L., Golczak, M., Doyle, S.E., McCall, M., Menaker, M., Palczewski, K., Van Gelder, R.N. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Hattar, S., Lucas, R.J., Mrosovsky, N., Thompson, S., Douglas, R.H., Hankins, M.W., Lem, J., Biel, M., Hofmann, F., Foster, R.G., Yau, K.W. Nature (2003) [Pubmed]
  8. A novel human opsin in the inner retina. Provencio, I., Rodriguez, I.R., Jiang, G., Hayes, W.P., Moreira, E.F., Rollag, M.D. J. Neurosci. (2000) [Pubmed]
  9. Induction of photosensitivity by heterologous expression of melanopsin. Qiu, X., Kumbalasiri, T., Carlson, S.M., Wong, K.Y., Krishna, V., Provencio, I., Berson, D.M. Nature (2005) [Pubmed]
  10. Expression of the candidate circadian photopigment melanopsin (Opn4) in the mouse retinal pigment epithelium. Peirson, S.N., Bovee-Geurts, P.H., Lupi, D., Jeffery, G., DeGrip, W.J., Foster, R.G. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  11. Melanopsin regulates visual processing in the mouse retina. Barnard, A.R., Hattar, S., Hankins, M.W., Lucas, R.J. Curr. Biol. (2006) [Pubmed]
  12. Melanopsin expression in the chick retina and pineal gland. Bailey, M.J., Cassone, V.M. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  13. Intrinsically photosensitive retinal ganglion cells detect light with a vitamin A-based photopigment, melanopsin. Fu, Y., Zhong, H., Wang, M.H., Luo, D.G., Liao, H.W., Maeda, H., Hattar, S., Frishman, L.J., Yau, K.W. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  14. Zebrafish melanopsin: isolation, tissue localisation and phylogenetic position. Bellingham, J., Whitmore, D., Philp, A.R., Wells, D.J., Foster, R.G. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  15. Dim light adaptation attenuates acute melatonin suppression in humans. Jasser, S.A., Hanifin, J.P., Rollag, M.D., Brainard, G.C. J. Biol. Rhythms (2006) [Pubmed]
  16. Light-induced c-fos in melanopsin retinal ganglion cells of young and aged rodless/coneless (rd/rd cl) mice. Semo, M., Lupi, D., Peirson, S.N., Butler, J.N., Foster, R.G. Eur. J. Neurosci. (2003) [Pubmed]
  17. Melanopsin--shedding light on the elusive circadian photopigment. Brown, R.L., Robinson, P.R. Chronobiol. Int. (2004) [Pubmed]
  18. Regulation of prokineticin 2 expression by light and the circadian clock. Cheng, M.Y., Bittman, E.L., Hattar, S., Zhou, Q.Y. BMC neuroscience [electronic resource]. (2005) [Pubmed]
  19. Melanopsin retinal ganglion cells and the maintenance of circadian and pupillary responses to light in aged rodless/coneless (rd/rd cl) mice. Semo, M., Peirson, S., Lupi, D., Lucas, R.J., Jeffery, G., Foster, R.G. Eur. J. Neurosci. (2003) [Pubmed]
  20. Axotomized mouse retinal ganglion cells containing melanopsin show enhanced survival, but not enhanced axon regrowth into a peripheral nerve graft. Robinson, G.A., Madison, R.D. Vision Res. (2004) [Pubmed]
  21. Effects of the prostaglandin E2 analogue enprostil on the carbon tetrachloride-induced necrosis of liver cells in mice. Bang, S., Myren, J., Linnestad, P., Serck-Hanssen, A., Strømme, J.H., Beraki, K. APMIS (1992) [Pubmed]
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