The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Nrl  -  neural retina leucine zipper gene

Mus musculus

Synonyms: AW492574, D14H14S46E, NRL, Neural retina-specific leucine zipper protein
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Nrl

  • Our studies provide molecular insights into differences between rod and cone function, yield interesting candidates for retinal diseases and assist in identifying transcriptional regulatory targets of Nrl [1].
  • Here, we show that retinoic acid (RA), a diffusible factor implicated in rod development, activates the expression of NRL in serum-deprived Y79 human retinoblastoma cells and in primary cultures of rat and porcine photoreceptors [2].
  • Ascites tumor cells BW-5147 were irradiated with a clinically usable fast neutron beam from the NRL cyclotron, which is produced by accelrating deuterons to 35 MeV and using htem to bombard a thick berylliumtarget [3].

High impact information on Nrl

  • On the basis of these findings, we postulate that Nrl acts as a 'molecular switch' during rod-cell development by directly modulating rod-specific genes while simultaneously inhibiting the S-cone pathway through the activation of Nr2e3 [4].
  • The photoreceptors in the Nrl-/- retina have cone-like nuclear morphology and short, sparse outer segments with abnormal disks [4].
  • The protein neural retina leucine zipper (Nrl) is a basic motif-leucine zipper transcription factor that is preferentially expressed in rod photoreceptors [4].
  • Analysis of retinal gene expression confirms the apparent functional transformation of rods into S cones in the Nrl-/- retina [4].
  • Nrl is required for rod photoreceptor development [4].

Biological context of Nrl


Anatomical context of Nrl

  • We show that a 2.5-kb Nrl promoter segment directs the expression of enhanced GFP specifically to rod photoreceptors and the pineal gland of transgenic mice [9].
  • The spatial pattern of hybridization suggests that Nrl is transcribed in post-mitotic, differentiating neurons, the developing cephalic mesenchyme and lens [8].
  • Nrl expression is downregulated postnatally in the brain, and becomes restricted to neocortex and brainstem in the adult [8].
  • We demonstrate that beginning at embryonic day 12.5 Nrl is expressed throughout the developing central and peripheral nervous system, with the exception of the nasal epithelium [8].
  • PURPOSE: To test the hypothesis that Nrl(-)(/)(-) photoreceptors are cones, by comparing them with WT rods and cones using morphological, molecular, histochemical, and electrophysiological criteria [10].

Associations of Nrl with chemical compounds

  • In Nrl(-/-) mice, different retinoid species were present in proportions similar to wild type [11].
  • Ablation of RPE65 in Nrl(-/-) and Rho(-/-) mice led to the absence of 11-cis retinal, but increased the total retinoid content, with retinyl esters representing the most abundant retinoid species [11].
  • We hypothesize that Bmp/Smad and Wnt/Ca(2+) pathways participate in cell-cell communication in the mature retina, and expression changes observed in the Nrl(-/-) retina reflect their biased utilization in rod versus cone homeostasis [12].

Regulatory relationships of Nrl

  • The basic motif-leucine zipper transcription factor Nrl can positively regulate rhodopsin gene expression [7].
  • Prompted by these findings, additional real-time PCR analysis revealed that genes belonging to the Bmp/Smad and Wnt/Ca(2+) signaling pathways are expressed in the mature wild type retina and that their expression is significantly altered in the Nrl(-/-) retina [12].

Other interactions of Nrl

  • In contrast, a Maf-related protein, Nrl, completely mimicked c-Maf actions [13].
  • In Nrl-/- retinas, the GFP+ photoreceptors express S-opsin, consistent with the transformation of rod precursors into cones [9].
  • Complexes binding the MARE in lens nuclear extracts are antigenically related to Nrl, and cotransfection with Nrl elevates zeta-crystallin promoter activity in lens cells [14].
  • In the current study, neural retina leucine zipper-deficient (Nrl(-/-)) and rod opsin (Rho(-/-))-deficient mice were used, two mouse models that have been described as having a "cone-only" retina, to analyze the retinoid metabolism of cones [11].
  • RESULTS: In comparison to wild-type mice, the retina of Nrl(-/-) mice contained elevated levels of RPE65 and cellular retinaldehyde-binding protein (CRALBP), suggesting a particular role of these two proteins for the retinoid metabolism of cones [11].

Analytical, diagnostic and therapeutic context of Nrl


  1. Expression profiling of the developing and mature Nrl-/- mouse retina: identification of retinal disease candidates and transcriptional regulatory targets of Nrl. Yoshida, S., Mears, A.J., Friedman, J.S., Carter, T., He, S., Oh, E., Jing, Y., Farjo, R., Fleury, G., Barlow, C., Hero, A.O., Swaroop, A. Hum. Mol. Genet. (2004) [Pubmed]
  2. Retinoic Acid Regulates the Expression of Photoreceptor Transcription Factor NRL. Khanna, H., Akimoto, M., Siffroi-Fernandez, S., Friedman, J.S., Hicks, D., Swaroop, A. J. Biol. Chem. (2006) [Pubmed]
  3. Fractionated dose of 35-MEV fast neutrons and hypoxic tumor cell survival curve. U, R., Evans, J.C., Cavanaugh, P.J., Abramson, N., Thompson, T.T., Wheless, D.M. Cancer (1975) [Pubmed]
  4. 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]
  5. 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]
  6. GRK1-dependent phosphorylation of S and M opsins and their binding to cone arrestin during cone phototransduction in the mouse retina. Zhu, X., Brown, B., Li, A., Mears, A.J., Swaroop, A., Craft, C.M. J. Neurosci. (2003) [Pubmed]
  7. The basic motif-leucine zipper transcription factor Nrl can positively regulate rhodopsin gene expression. Rehemtulla, A., Warwar, R., Kumar, R., Ji, X., Zack, D.J., Swaroop, A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  8. Expression of the bZIP transcription factor gene Nrl in the developing nervous system. Liu, Q., Ji, X., Breitman, M.L., Hitchcock, P.F., Swaroop, A. Oncogene (1996) [Pubmed]
  9. Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors. Akimoto, M., Cheng, H., Zhu, D., Brzezinski, J.A., Khanna, R., Filippova, E., Oh, E.C., Jing, Y., Linares, J.L., Brooks, M., Zareparsi, S., Mears, A.J., Hero, A., Glaser, T., Swaroop, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  10. Cone-like morphological, molecular, and electrophysiological features of the photoreceptors of the Nrl knockout mouse. Daniele, L.L., Lillo, C., Lyubarsky, A.L., Nikonov, S.S., Philp, N., Mears, A.J., Swaroop, A., Williams, D.S., Pugh, E.N. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  11. RPE65 Is Essential for the Function of Cone Photoreceptors in NRL-Deficient Mice. Wenzel, A., von Lintig, J., Oberhauser, V., Tanimoto, N., Grimm, C., Seeliger, M.W. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  12. Altered expression of genes of the Bmp/Smad and Wnt/calcium signaling pathways in the cone-only Nrl-/- mouse retina, revealed by gene profiling using custom cDNA microarrays. Yu, J., He, S., Friedman, J.S., Akimoto, M., Ghosh, D., Mears, A.J., Hicks, D., Swaroop, A. J. Biol. Chem. (2004) [Pubmed]
  13. The maf proto-oncogene stimulates transcription from multiple sites in a promoter that directs Purkinje neuron-specific gene expression. Kurschner, C., Morgan, J.I. Mol. Cell. Biol. (1995) [Pubmed]
  14. Lens-specific gene recruitment of zeta-crystallin through Pax6, Nrl-Maf, and brain suppressor sites. Sharon-Friling, R., Richardson, J., Sperbeck, S., Lee, D., Rauchman, M., Maas, R., Swaroop, A., Wistow, G. Mol. Cell. Biol. (1998) [Pubmed]
  15. FIZ1 is expressed during photoreceptor maturation, and synergizes with NRL and CRX at rod-specific promoters in vitro. Mali, R.S., Zhang, X., Hoerauf, W., Doyle, D., Devitt, J., Loffreda-Wren, J., Mitton, K.P. Exp. Eye Res. (2007) [Pubmed]
WikiGenes - Universities