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Gene Review

Crx  -  cone-rod homeobox

Mus musculus

Synonyms: Cone-rod homeobox protein, Crx1
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Disease relevance of Crx


High impact information on Crx

  • In the mouse, targeted inactivation of Crx causes a reduction in pineal gene expression and attenuated entrainment to light/dark cycles [4].
  • It acts synergistically with Crx to regulate rhodopsin transcription [5].
  • Crx-/- mice do not elaborate photoreceptor outer segments and lacked rod and cone activity as assayed by electroretinogram (ERG) [6].
  • Crx has been proposed to have a role in the regulation of photoreceptor-specific genes in the eye and of pineal-specific genes in the pineal gland [6].
  • Overexpression of Crx using a retroviral vector increased the frequency of clones containing exclusively rod photoreceptors and reduced the frequency of clones containing amacrine interneurons and Müller glial cells [7].

Biological context of Crx


Anatomical context of Crx

  • Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes [1].
  • Altogether, our findings suggest that Nr2e3 is a dual-function transcriptional regulator that acts in concert with Crx to promote and maintain the function of rod photoreceptors [8].
  • The paired-type homeobox transcription factor, Crx, has a pivotal role in the terminal differentiation of vertebrate photoreceptors [10].
  • In HeLa cells transfected with these promoters, co-transfection of a Crx expression vector with wild-type, but not with CRXE mutant promoter, activates CAT activity 20-fold over the background activity [11].

Associations of Crx with chemical compounds

  • Crx also binds to and transactivates the genes for several other photoreceptor cell-specific proteins (interphotoreceptor retinoid-binding protein, beta-phosphodiesterase, and arrestin) [1].
  • In an SCA7 transgenic mouse model that we developed, it was found that the cone-rod dystrophy involves altered photoreceptor gene expression due to interference with Crx, a homeodomain transcription factor containing a glutamine-rich region [2].
  • Developmentally regulated expression of GABA receptor rho1 and rho2 subunits, L7 and cone-rod homeobox (CRX) genes in mouse retina [12].

Physical interactions of Crx

  • Several mutant forms of human Nr2e3 identified from ESCS patients showed defects in interacting with Crx and/or in transcriptional regulatory function [8].
  • Recombinant Crx binds in vitro not only to the Ret 4 site but also to the Ret 1 and BAT-1 sites [1].

Regulatory relationships of Crx


Other interactions of Crx

  • We also found that Otx2 transactivates the cone-rod homeobox gene Crx, which is required for terminal differentiation and maintenance of photoreceptor cells [15].
  • Development of several new SSLP markers allowed us to refine the hyh candidate interval to a region defined by the cone-rod homeobox ( Crx) gene proximally and D7Mit56 distally [16].
  • The most active segment contained a 177-bp upstream sequence including apparent Crx and Nrl transcription factor binding sites [9].
  • In addition, we overexpressed another NAT, CrxOS, in mouse adult retina using adeno-associated viral vectors and we observed a significant decrease in the expression levels of the corresponding sense gene, Crx [17].
  • Functional analysis of the rod photoreceptor cGMP phosphodiesterase alpha-subunit gene promoter: Nrl and Crx are required for full transcriptional activity [9].

Analytical, diagnostic and therapeutic context of Crx


  1. Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes. Chen, S., Wang, Q.L., Nie, Z., Sun, H., Lennon, G., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Zack, D.J. Neuron (1997) [Pubmed]
  2. Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization. Chen, S., Peng, G.H., Wang, X., Smith, A.C., Grote, S.K., Sopher, B.L., La Spada, A.R. Hum. Mol. Genet. (2004) [Pubmed]
  3. Mouse cone arrestin gene characterization: promoter targets expression to cone photoreceptors. Zhu, X., Ma, B., Babu, S., Murage, J., Knox, B.E., Craft, C.M. FEBS Lett. (2002) [Pubmed]
  4. Otx5 regulates genes that show circadian expression in the zebrafish pineal complex. Gamse, J.T., Shen, Y.C., Thisse, C., Thisse, B., Raymond, P.A., Halpern, M.E., Liang, J.O. Nat. Genet. (2002) [Pubmed]
  5. Nrl is required for rod photoreceptor development. Mears, A.J., Kondo, M., Swain, P.K., Takada, Y., Bush, R.A., Saunders, T.L., Sieving, P.A., Swaroop, A. Nat. Genet. (2001) [Pubmed]
  6. Retinopathy and attenuated circadian entrainment in Crx-deficient mice. Furukawa, T., Morrow, E.M., Li, T., Davis, F.C., Cepko, C.L. Nat. Genet. (1999) [Pubmed]
  7. Crx, a novel otx-like homeobox gene, shows photoreceptor-specific expression and regulates photoreceptor differentiation. Furukawa, T., Morrow, E.M., Cepko, C.L. Cell (1997) [Pubmed]
  8. The photoreceptor-specific nuclear receptor Nr2e3 interacts with Crx and exerts opposing effects on the transcription of rod versus cone genes. Peng, G.H., Ahmad, O., Ahmad, F., Liu, J., Chen, S. Hum. Mol. Genet. (2005) [Pubmed]
  9. Functional analysis of the rod photoreceptor cGMP phosphodiesterase alpha-subunit gene promoter: Nrl and Crx are required for full transcriptional activity. Pittler, S.J., Zhang, Y., Chen, S., Mears, A.J., Zack, D.J., Ren, Z., Swain, P.K., Yao, S., Swaroop, A., White, J.B. J. Biol. Chem. (2004) [Pubmed]
  10. Microarray analysis of the transcriptional network controlled by the photoreceptor homeobox gene Crx. Livesey, F.J., Furukawa, T., Steffen, M.A., Church, G.M., Cepko, C.L. Curr. Biol. (2000) [Pubmed]
  11. Functional dissection of the promoter of the interphotoreceptor retinoid-binding protein gene: the cone-rod-homeobox element is essential for photoreceptor-specific expression in vivo. Fei, Y., Matragoon, S., Smith, S.B., Overbeek, P.A., Chen, S., Zack, D.J., Liou, G.I. J. Biochem. (1999) [Pubmed]
  12. Developmentally regulated expression of GABA receptor rho1 and rho2 subunits, L7 and cone-rod homeobox (CRX) genes in mouse retina. Wu, Y., Cutting, G.R. Brain Res. (2001) [Pubmed]
  13. Leukemia inhibitory factor blocks expression of Crx and Nrl transcription factors to inhibit photoreceptor differentiation. Graham, D.R., Overbeek, P.A., Ash, J.D. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  14. Cytokine-induced activation of signal transducer and activator of transcription in photoreceptor precursors regulates rod differentiation in the developing mouse retina. Rhee, K.D., Goureau, O., Chen, S., Yang, X.J. J. Neurosci. (2004) [Pubmed]
  15. Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development. Nishida, A., Furukawa, A., Koike, C., Tano, Y., Aizawa, S., Matsuo, I., Furukawa, T. Nat. Neurosci. (2003) [Pubmed]
  16. Mapping of the mouse hyh gene to a YAC/BAC contig on proximal Chromosome 7. Chae, T.H., Allen, K.M., Davisson, M.T., Sweet, H.O., Walsh, C.A. Mamm. Genome (2002) [Pubmed]
  17. Natural antisense transcripts associated with genes involved in eye development. Alfano, G., Vitiello, C., Caccioppoli, C., Caramico, T., Carola, A., Szego, M.J., McInnes, R.R., Auricchio, A., Banfi, S. Hum. Mol. Genet. (2005) [Pubmed]
  18. Delayed expression of the Crx gene and photoreceptor development in the Chx10-deficient retina. Rutherford, A.D., Dhomen, N., Smith, H.K., Sowden, J.C. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  19. Inner retinal abnormalities in a mouse model of Leber's congenital amaurosis. Pignatelli, V., Cepko, C.L., Strettoi, E. J. Comp. Neurol. (2004) [Pubmed]
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