Gene Symbol: Ndp
Description: Norrie disease (pseudoglioma) (human)
Alias: Ndph, norrin, norrie disease protein homolog
Species: mouse
Products:     Ndp

Top Publications

  1. Schäfer N, Luhmann U, Feil S, Berger W. Differential gene expression in Ndph-knockout mice in retinal development. Invest Ophthalmol Vis Sci. 2009;50:906-16 pubmed publisher
    ..This study was conducted to investigate the differential gene expression caused by the absence of Norrin (the NDP protein) in the developing mouse retina and to elucidate early pathogenic events...
  2. Berger W. Molecular dissection of Norrie disease. Acta Anat (Basel). 1998;162:95-100 pubmed
    ..Further histological, functional and molecular studies of the mouse model are needed to provide additional information on disease associated pathways...
  3. Deng C, Reddy P, Cheng Y, Luo C, Hsiao C, Hsueh A. Multi-functional norrin is a ligand for the LGR4 receptor. J Cell Sci. 2013;126:2060-8 pubmed publisher
    ..Using newly available genome sequences, we showed that norrin is a vertebrate ortholog for insect burs and pburs and stimulates Wnt signaling mediated by LGR4, but not by LGR5 ..
  4. Luhmann U, Lin J, Acar N, Lammel S, Feil S, Grimm C, et al. Role of the Norrie disease pseudoglioma gene in sprouting angiogenesis during development of the retinal vasculature. Invest Ophthalmol Vis Sci. 2005;46:3372-82 pubmed
    ..These data provide evidence for a crucial role of Norrin in hyaloid vessel regression and in sprouting angiogenesis during retinal vascular development, especially in the ..
  5. Xu Q, Wang Y, Dabdoub A, Smallwood P, Williams J, Woods C, et al. Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell. 2004;116:883-95 pubmed
    Incomplete retinal vascularization occurs in both Norrie disease and familial exudative vitreoretinopathy (FEVR). Norrin, the protein product of the Norrie disease gene, is a secreted protein of unknown biochemical function...
  6. Ye X, Wang Y, Cahill H, Yu M, Badea T, Smallwood P, et al. Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization. Cell. 2009;139:285-98 pubmed publisher
    ..Mutations in the Frizzled-4 (Fz4) receptor, Lrp5 coreceptor, or Norrin ligand cause retinal hypovascularization, but the mechanisms by which Norrin/Fz4/Lrp signaling controls vascular ..
  7. Berger W, van de Pol D, Bächner D, Oerlemans F, Winkens H, Hameister H, et al. An animal model for Norrie disease (ND): gene targeting of the mouse ND gene. Hum Mol Genet. 1996;5:51-9 pubmed
    ..These ocular findings are consistent with observations in ND patients and the generated mouse line provides a faithful model for study of early pathogenic events in this severe X-linked recessive neurological disorder. ..
  8. Braunger B, Ohlmann A, Koch M, Tanimoto N, Volz C, Yang Y, et al. Constitutive overexpression of Norrin activates Wnt/?-catenin and endothelin-2 signaling to protect photoreceptors from light damage. Neurobiol Dis. 2013;50:1-12 pubmed publisher
    b>Norrin is a retinal signaling molecule which is expressed in Müller glia and binds to Frizzled-4 to activate canonical Wnt/?-catenin signaling...
  9. Bassett E, Tokarew N, Allemano E, Mazerolle C, Morin K, Mears A, et al. Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation. elife. 2016;5: pubmed publisher
    ..We show that activation of the vascular regulatory signalling axis mediated by Norrin (an atypical Wnt)/Frizzled4 (Fzd4) inhibits MB initiation in the Ptch+/- mouse model...

More Information


  1. Battinelli E, Boyd Y, Craig I, Breakefield X, Chen Z. Characterization and mapping of the mouse NDP (Norrie disease) locus (Ndp). Mamm Genome. 1996;7:93-7 pubmed
    ..Over half of Norrie patients also manifest different degrees of mental retardation. The gene for Norrie disease (NDP) has recently been cloned and characterized...
  2. Makałowski W, Zhang J, Boguski M. Comparative analysis of 1196 orthologous mouse and human full-length mRNA and protein sequences. Genome Res. 1996;6:846-57 pubmed
    ..Also, they should prove useful in estimating the additional sampling diversity provided by mouse EST sequencing projects designed to complement the existing human cDNA collection. ..
  3. Ohlmann A, Adamek E, Ohlmann A, Lütjen Drecoll E. Norrie gene product is necessary for regression of hyaloid vessels. Invest Ophthalmol Vis Sci. 2004;45:2384-90 pubmed
    ..The ND gene product neither influences endostatin expression nor the presence of macrophages. ..
  4. McNeill B, Mazerolle C, Bassett E, Mears A, Ringuette R, Lagali P, et al. Hedgehog regulates Norrie disease protein to drive neural progenitor self-renewal. Hum Mol Genet. 2013;22:1005-16 pubmed publisher
    ..ND has been linked to mutations in 'Norrie Disease Protein' (Ndp), which encodes the secreted protein Norrin. Norrin functions as a secreted angiogenic factor, although its role in neural development has not been assessed...
  5. Braunger B, Tamm E. The different functions of Norrin. Adv Exp Med Biol. 2012;723:679-83 pubmed publisher
  6. Luhmann U, Neidhardt J, Kloeckener Gruissem B, Schäfer N, Glaus E, Feil S, et al. Vascular changes in the cerebellum of Norrin /Ndph knockout mice correlate with high expression of Norrin and Frizzled-4. Eur J Neurosci. 2008;27:2619-28 pubmed publisher
    ..In the present study, we analysed transcript levels of the ligand Norrin (Ndph) and its two receptors Frizzled-4 (Fzd4) and LDL-related protein receptor 5 (Lrp5) in six different brain ..
  7. Wollmann G, Lenzner S, Berger W, Rosenthal R, Karl M, Strauss O. Voltage-dependent ion channels in the mouse RPE: comparison with Norrie disease mice. Vision Res. 2006;46:688-98 pubmed
    ..Although no significant differences were observed, our study provides a base for future studies on ion channel function and dysfunction in transgenic mouse models. ..
  8. Lee H, Jo D, Kim J, Kim J. Norrin expression in endothelial cells in the developing mouse retina. Acta Histochem. 2013;115:447-51 pubmed publisher
    b>Norrin, a protein that acts on Frizzled-4 receptor, participates in angiogenesis in a variety of contexts through the Wnt-signaling pathway. Specifically, Norrin is found to play a crucial role in retinal vascularization...
  9. Rehm H, Zhang D, Brown M, Burgess B, Halpin C, Berger W, et al. Vascular defects and sensorineural deafness in a mouse model of Norrie disease. J Neurosci. 2002;22:4286-92 pubmed
    ..We propose that one of the principal functions of norrin in the ear is to regulate the interaction of the cochlea with its vasculature.
  10. Ke J, Harikumar K, Erice C, Chen C, Gu X, Wang L, et al. Structure and function of Norrin in assembly and activation of a Frizzled 4-Lrp5/6 complex. Genes Dev. 2013;27:2305-19 pubmed publisher
    b>Norrin is a cysteine-rich growth factor that is required for angiogenesis in the eye, ear, brain, and female reproductive organs. It functions as an atypical Wnt ligand by specifically binding to the Frizzled 4 (Fz4) receptor...
  11. Chen J, Stahl A, Krah N, Seaward M, Joyal J, Juan A, et al. Retinal expression of Wnt-pathway mediated genes in low-density lipoprotein receptor-related protein 5 (Lrp5) knockout mice. PLoS ONE. 2012;7:e30203 pubmed publisher
    ..Together these data suggest that Lrp5 regulates multiple groups of genes that influence retinal angiogenesis and may contribute to the pathogenesis of FEVR. ..
  12. Zhou Y, Wang Y, TISCHFIELD M, Williams J, Smallwood P, Rattner A, et al. Canonical WNT signaling components in vascular development and barrier formation. J Clin Invest. 2014;124:3825-46 pubmed publisher
    ..Brain and retinal vascular defects resulting from ablation of Norrin/Frizzled4 signaling were ameliorated by stabilizing ?-catenin, while inhibition of ?-catenin-dependent ..
  13. Rattner A, Wang Y, Zhou Y, Williams J, Nathans J. The role of the hypoxia response in shaping retinal vascular development in the absence of Norrin/Frizzled4 signaling. Invest Ophthalmol Vis Sci. 2014;55:8614-25 pubmed publisher
    ..VEGF) in modifying the pattern, density, and permeability of the retinal vasculature in mouse models in which Norrin/Frizzled4 signaling is impaired...
  14. Einerhand M, Bakx T, Valerio D. IL-6 production by retrovirus packaging cells and cultured bone marrow cells. Hum Gene Ther. 1991;2:301-6 pubmed
    ..Considering that IL-6 is produced in large amounts during co-cultivations, we believe that its effect on the transduction of HSC cannot be measured by adding extra growth factor to the co-culture medium. ..
  15. Luhmann U, Meunier D, Shi W, Lüttges A, Pfarrer C, Fundele R, et al. Fetal loss in homozygous mutant Norrie disease mice: a new role of Norrin in reproduction. Genesis. 2005;42:253-62 pubmed
    ..such as familial exudative vitreoretinopathy, retinopathy of prematurity, and Coats disease, suggesting a role for Norrin in vascular development...
  16. Cho C, Smallwood P, Nathans J. Reck and Gpr124 Are Essential Receptor Cofactors for Wnt7a/Wnt7b-Specific Signaling in Mammalian CNS Angiogenesis and Blood-Brain Barrier Regulation. Neuron. 2017;95:1056-1073.e5 pubmed publisher
    ..reduction in Reck impairs CNS angiogenesis and that EC-specific postnatal loss of Reck, combined with loss of Norrin, impairs blood-brain barrier (BBB) maintenance...
  17. Hsieh M, Boerboom D, Shimada M, Lo Y, Parlow A, Luhmann U, et al. Mice null for Frizzled4 (Fzd4-/-) are infertile and exhibit impaired corpora lutea formation and function. Biol Reprod. 2005;73:1135-46 pubmed
    ..Although a recently identified, high-affinity FZD4 ligand Norrin (Norrie disease pseudoglioma homolog) is expressed in the ovary, adult Ndph-/- mice contain functional corpora ..
  18. Zhou Y, Nathans J. Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by promoting ligand-specific canonical wnt signaling. Dev Cell. 2014;31:248-56 pubmed publisher
    ..via a Frizzled receptor and Lrp coreceptor and that Gpr124-stimulated signaling functions in concert with Norrin/Frizzled4 signaling to control CNS vascular development...
  19. Seitz R, Hackl S, Seibuchner T, Tamm E, Ohlmann A. Norrin mediates neuroprotective effects on retinal ganglion cells via activation of the Wnt/beta-catenin signaling pathway and the induction of neuroprotective growth factors in Muller cells. J Neurosci. 2010;30:5998-6010 pubmed publisher
    b>Norrin is a secreted protein that binds to frizzled 4 and controls development of capillaries in retina and inner ear...
  20. Wang Y, Rattner A, Zhou Y, Williams J, Smallwood P, Nathans J. Norrin/Frizzled4 signaling in retinal vascular development and blood brain barrier plasticity. Cell. 2012;151:1332-44 pubmed publisher
    b>Norrin/Frizzled4 (Fz4) signaling activates the canonical Wnt pathway to control retinal vascular development...
  21. Sims K, Lebo R, Benson G, Shalish C, Schuback D, Chen Z, et al. The Norrie disease gene maps to a 150 kb region on chromosome Xp11.3. Hum Mol Genet. 1992;1:83-9 pubmed
    ..3. We report here fine physical mapping of the obligate region containing the Norrie disease gene (NDP) defined by a recombination and by the smallest submicroscopic chromosomal deletion associated with Norrie disease ..
  22. Hartzer M, Cheng M, Liu X, Shastry B. Localization of the Norrie disease gene mRNA by in situ hybridization. Brain Res Bull. 1999;49:355-8 pubmed
    ..These data suggest that the Norrie disease gene could play a critical role in the differentiation or maintenance of the differentiated state of the retina. ..
  23. Lenzner S, Prietz S, Feil S, Nuber U, Ropers H, Berger W. Global gene expression analysis in a mouse model for Norrie disease: late involvement of photoreceptor cells. Invest Ophthalmol Vis Sci. 2002;43:2825-33 pubmed
    Mutations in the NDP gene give rise to a variety of eye diseases, including classic Norrie disease (ND), X-linked exudative vitreoretinopathy (EVRX), retinal telangiectasis (Coats disease), and advanced retinopathy of prematurity (ROP)...
  24. Welge Lussen U, Wilsch C, Neuhardt T, Wayne Streilein J, Lütjen Drecoll E. Loss of anterior chamber-associated immune deviation (ACAID) in aged retinal degeneration (rd) mice. Invest Ophthalmol Vis Sci. 1999;40:3209-14 pubmed
    ..Because loss of ACAID correlated with a decrease in TGF-beta2 concentration in aqueous humor, it is proposed that eyes of rd mice are unable to maintain an immunosuppressive microenvironment necessary for ACAID. ..
  25. Ohlmann A, Scholz M, Goldwich A, Chauhan B, Hudl K, Ohlmann A, et al. Ectopic norrin induces growth of ocular capillaries and restores normal retinal angiogenesis in Norrie disease mutant mice. J Neurosci. 2005;25:1701-10 pubmed
    ..b>Norrin, the protein product of the Norrie disease gene (NDP), is a secreted protein of unknown biochemical function...
  26. Richter M, Gottanka J, May C, Welge Lussen U, Berger W, Lütjen Drecoll E. Retinal vasculature changes in Norrie disease mice. Invest Ophthalmol Vis Sci. 1998;39:2450-7 pubmed
    ..It is assumed that the ND gene product is required for normal vascularization of the inner retinal layers and for atrophy of hyaloid vessels. ..
  27. Junge H, Yang S, Burton J, Paes K, Shu X, French D, et al. TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/beta-catenin signaling. Cell. 2009;139:299-311 pubmed publisher
    Mutations in the genes encoding the Wnt receptor Frizzled-4 (FZD4), coreceptor LRP5, or the ligand Norrin disrupt retinal vascular development and cause ophthalmic diseases...
  28. Hsu P, Wu F, Kudo M, Hsiao C, Hsueh A, Luo C. A naturally occurring Lgr4 splice variant encodes a soluble antagonist useful for demonstrating the gonadal roles of Lgr4 in mammals. PLoS ONE. 2014;9:e106804 pubmed publisher
    ..containing G protein-coupled receptor 4 (LGR4) promotes the Wnt signaling through interaction with R-spondins or norrin. Using PCR amplification from rat ovarian cDNAs, we identified a naturally occurring Lgr4 splice variant encoding ..
  29. Zuercher J, Fritzsche M, Feil S, Mohn L, Berger W. Norrin stimulates cell proliferation in the superficial retinal vascular plexus and is pivotal for the recruitment of mural cells. Hum Mol Genet. 2012;21:2619-30 pubmed publisher
    Mutations in Norrin, the ligand of a receptor complex consisting of FZD4, LRP5 and TSPAN12, cause severe developmental blood vessel defects in the retina and progressive loss of the vascular system in the inner ear, which lead to ..
  30. Ruether K, van de Pol D, Jaissle G, Berger W, Tornow R, Zrenner E. Retinoschisislike alterations in the mouse eye caused by gene targeting of the Norrie disease gene. Invest Ophthalmol Vis Sci. 1997;38:710-8 pubmed
    ..These findings may be a clue to the embryonal retinoschisislike pathogenesis of Norrie disease in humans or it may indicate a different expression of the Norrie disease gene defect in mice compared to that in humans. ..
  31. Ye X, Smallwood P, Nathans J. Expression of the Norrie disease gene (Ndp) in developing and adult mouse eye, ear, and brain. Gene Expr Patterns. 2011;11:151-5 pubmed publisher
    The Norrie disease gene (Ndp) codes for a secreted protein, Norrin, that activates canonical Wnt signaling by binding to its receptor, Frizzled-4...