Gene Symbol: Dkk3
Description: dickkopf WNT signaling pathway inhibitor 3
Alias: AW061014, C87148, dkk-3, mDkk-3, dickkopf-related protein 3, dickkopf homolog 3, dickkopf-3
Species: mouse
Products:     Dkk3

Top Publications

  1. Monaghan A, Kioschis P, Wu W, Zuniga A, Bock D, Poustka A, et al. Dickkopf genes are co-ordinately expressed in mesodermal lineages. Mech Dev. 1999;87:45-56 pubmed
    ..Our observations indicate that dkk genes constitute a new family of secreted proteins that may mediate inductive interactions between epithelial and mesenchymal cells. ..
  2. Aslan H, Ravid Amir O, Clancy B, Rezvankhah S, Pittman D, Pelled G, et al. Advanced molecular profiling in vivo detects novel function of dickkopf-3 in the regulation of bone formation. J Bone Miner Res. 2006;21:1935-45 pubmed
    ..Among these genes the dickkopf homolog 3 (Dkk3) was upregulated and further studies showed that its expression affects in vitro and in vivo ..
  3. Ang S, Stump R, Lovicu F, McAvoy J. Spatial and temporal expression of Wnt and Dickkopf genes during murine lens development. Gene Expr Patterns. 2004;4:289-95 pubmed
    ..This is most notable for Wnt5a, which is barely detectable in the central lens epithelium at P21. Dkk1, Dkk2 and Dkk3 have similar patterns of expression to each other and to the majority of the Wnts during lens development...
  4. Diep D, Hoen N, Backman M, Machon O, Krauss S. Characterisation of the Wnt antagonists and their response to conditionally activated Wnt signalling in the developing mouse forebrain. Brain Res Dev Brain Res. 2004;153:261-70 pubmed
    ..In situ hybridisation on sections from E12 embryos showed an expression of dkk2 in the thalamus and dkk3 in the cortical hem and thalamus. At later developmental stages (E15.5, E17...
  5. Nakamura R, Hunter D, Yi H, Brunken W, Hackam A. Identification of two novel activities of the Wnt signaling regulator Dickkopf 3 and characterization of its expression in the mouse retina. BMC Cell Biol. 2007;8:52 pubmed
    ..1 (Dkk1) and Dickkopf 2 (Dkk2) are well characterized, little is known about the function of the related Dickkopf 3 (Dkk3) protein in vivo or in cell lines...
  6. Sato S, Inoue T, Terada K, Matsuo I, Aizawa S, Tano Y, et al. Dkk3-Cre BAC transgenic mouse line: a tool for highly efficient gene deletion in retinal progenitor cells. Genesis. 2007;45:502-7 pubmed
    To establish the genetic tools for conditional gene deletion in mouse retinal progenitors, we generated a Dkk3-Cre transgenic mouse line using bacterial artificial chromosome (BAC) transgenesis...
  7. Krupnik V, Sharp J, Jiang C, Robison K, Chickering T, Amaravadi L, et al. Functional and structural diversity of the human Dickkopf gene family. Gene. 1999;238:301-13 pubmed
    ..Thus, hDkks 1 and 4 may inhibit Wnt activity by a mechanism upstream of Frizzled. Our findings highlight the structural and functional heterogeneity of human Dkk-related proteins. ..
  8. Barrantes I, Montero Pedrazuela A, Guadaño Ferraz A, Obregon M, Martinez de Mena R, Gailus Durner V, et al. Generation and characterization of dickkopf3 mutant mice. Mol Cell Biol. 2006;26:2317-26 pubmed
    dickkopf (dkk) genes encode a small family of secreted Wnt antagonists, except for dkk3, which is divergent and whose function is poorly understood. Here, we describe the generation and characterization of dkk3 mutant mice...
  9. Yu B, Kiechl S, Qi D, Wang X, Song Y, Weger S, et al. A Cytokine-Like Protein Dickkopf-Related Protein 3 Is Atheroprotective. Circulation. 2017;136:1022-1036 pubmed publisher
    Dickkopf-related protein 3 (DKK3) is a secreted protein that is involved in the regulation of cardiac remodeling and vascular smooth muscle cell differentiation, but little is known about its role in atherosclerosis...

More Information


  1. Nie X, Luukko K, Fjeld K, Kvinnsland I, Kettunen P. Developmental expression of Dkk1-3 and Mmp9 and apoptosis in cranial base of mice. J Mol Histol. 2005;36:419-26 pubmed
    ..Dkk2 was localized in the perichondral mesenchyme outlining the anterior cranial base in embryogenesis. Dkk3 was mainly detected in the occipital-vertebral joint at E13 and E14...
  2. Utreja A, Dyment N, Yadav S, Villa M, Li Y, Jiang X, et al. Cell and matrix response of temporomandibular cartilage to mechanical loading. Osteoarthritis Cartilage. 2016;24:335-44 pubmed publisher
    ..Four-week-old transgenic mice harboring combinations of fluorescent reporters (Dkk3-eGFP, Col1a1(3.6 kb)-GFPcyan, Col1a1(3...
  3. Lu D, Bao D, Dong W, Liu N, Zhang X, Gao S, et al. Dkk3 prevents familial dilated cardiomyopathy development through Wnt pathway. Lab Invest. 2016;96:239-48 pubmed publisher
    To date, the role of Dickkopf 3 (Dkk3) on the pathogenesis of familial dilated cardiomyopathy (FDCM), and whether and how Dkk3 interferes with Wnt signaling in heart tissues remains unknown...
  4. Decker R, Um H, Dyment N, Cottingham N, Usami Y, Enomoto Iwamoto M, et al. Cell origin, volume and arrangement are drivers of articular cartilage formation, morphogenesis and response to injury in mouse limbs. Dev Biol. 2017;426:56-68 pubmed publisher
    ..Using novel Gdf5CreERT2 (Gdf5-CE), Prg4-CE and Dkk3-CE mice mated to R26-Confetti or single-color reporters, we found that knee joint progenitors produced small non-..
  5. Schmolka N, Serre K, Grosso A, Rei M, Pennington D, Gomes A, et al. Epigenetic and transcriptional signatures of stable versus plastic differentiation of proinflammatory γδ T cell subsets. Nat Immunol. 2013;14:1093-1100 pubmed publisher
  6. Kole C, Berdugo N, Da Silva C, Aït Ali N, Millet Puel G, Pagan D, et al. Identification of an Alternative Splicing Product of the Otx2 Gene Expressed in the Neural Retina and Retinal Pigmented Epithelial Cells. PLoS ONE. 2016;11:e0150758 pubmed publisher
    ..We find that OTX2S is able to bind to the chromatin at the promoter of the retinal dehydrogenase 10 (RDH10) gene. ..
  7. Ludwig J, Federico G, Prokosch S, Küblbeck G, Schmitt S, Klevenz A, et al. Dickkopf-3 acts as a modulator of B cell fate and function. J Immunol. 2015;194:2624-34 pubmed publisher
    ..In this study, we demonstrated that absence of Dickkopf-3 (DKK3) led to changes in the composition of the B cell compartment, which were due to an altered development and ..
  8. Kudo L, Karsten S, Chen J, Levitt P, Geschwind D. Genetic analysis of anterior posterior expression gradients in the developing mammalian forebrain. Cereb Cortex. 2007;17:2108-22 pubmed
    ..These data provide an important set of new candidates for studies of cortical patterning and maturation. ..
  9. Federico G, Meister M, Mathow D, Heine G, Moldenhauer G, Popovic Z, et al. Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis. JCI Insight. 2016;1:e84916 pubmed
    ..Here, we identify DKK3 as a stress-induced, tubular epithelia-derived, secreted glycoprotein that mediates kidney fibrosis...
  10. Fjeld K, Kettunen P, Furmanek T, Kvinnsland I, Luukko K. Dynamic expression of Wnt signaling-related Dickkopf1, -2, and -3 mRNAs in the developing mouse tooth. Dev Dyn. 2005;233:161-6 pubmed
    ..Dkk2 was seen in the dental papilla, whereas Dkk3 was specifically expressed in the putative epithelial signaling centers, the primary and secondary enamel knots...
  11. El Wakil A, Bandulik S, Guy N, Bendahhou S, Zennaro M, Niehrs C, et al. Dkk3 is a component of the genetic circuitry regulating aldosterone biosynthesis in the adrenal cortex. Hum Mol Genet. 2012;21:4922-9 pubmed publisher
    ..Genetic inactivation of one of the genes identified by our strategy, dickkopf-3 (Dkk3), whose expression is increased by calcium influx into adrenocortical cells, in the Kcnk3 null background results ..
  12. Porntaveetus T, Ohazama A, Choi H, Herz J, Sharpe P. Wnt signaling in the murine diastema. Eur J Orthod. 2012;34:518-24 pubmed publisher
    ..Secreted Wnt inihibitors Dkk1, Dkk2, and Dkk3 were also expressed in the diastema...
  13. Cheng W, Yang Y, Zhang X, Guo J, Gong J, Gong F, et al. Dickkopf-3 Ablation Attenuates the Development of Atherosclerosis in ApoE-Deficient Mice. J Am Heart Assoc. 2017;6: pubmed publisher
    Dickkopf-3 (DKK3) is a negative regulator of the Wnt/β-catenin signaling pathway, which is involved in inflammation. However, little is known about the relationship between DKK3 expression and the progression of atherosclerosis...
  14. Woodworth M, Greig L, Liu K, Ippolito G, Tucker H, Macklis J. Ctip1 Regulates the Balance between Specification of Distinct Projection Neuron Subtypes in Deep Cortical Layers. Cell Rep. 2016;15:999-1012 pubmed publisher
    ..Therefore, Ctip1 couples subtype and area specification, enabling specific functional areas to organize precise ratios of appropriate output projections. ..
  15. Du G, Kataoka K, Sakaguchi M, Abarzua F, Than S, Sonegawa H, et al. Expression of REIC/Dkk-3 in normal and hyperproliferative epidermis. Exp Dermatol. 2011;20:273-7 pubmed publisher
    ..REIC/Dkk-3 expression was also suppressed in the regenerative and inflammative epidermis of model mice. These findings will certainly contribute to the extension of studies on REIC/Dkk-3. ..
  16. Wang X, Karamariti E, Simpson R, Wang W, Xu Q. Dickkopf Homolog 3 Induces Stem Cell Differentiation into Smooth Muscle Lineage via ATF6 Signalling. J Biol Chem. 2015;290:19844-52 pubmed publisher
    ..Previous studies suggested that dickkopf homolog 3 (DKK3) has a role in human partially induced pluripotent stem cell to SMC differentiation...
  17. Bharti K, Gasper M, Ou J, Brucato M, Clore Gronenborn K, Pickel J, et al. A regulatory loop involving PAX6, MITF, and WNT signaling controls retinal pigment epithelium development. PLoS Genet. 2012;8:e1002757 pubmed publisher
    ..expression analyses show that, together with MITF or its paralog TFEC, PAX6 suppresses the expression of Fgf15 and Dkk3. Explant culture experiments indicate that a combination of FGF and DKK3 promote retina formation by inhibiting ..
  18. Villavicencio Lorini P, Kuss P, Friedrich J, Haupt J, Farooq M, Turkmen S, et al. Homeobox genes d11-d13 and a13 control mouse autopod cortical bone and joint formation. J Clin Invest. 2010;120:1994-2004 pubmed publisher
    ..These data indicate that Hox genes not only regulate patterning but also directly influence bone formation and the ossification pattern of bones, in part via Runx2. ..
  19. De Langhe S, Sala F, del Moral P, Fairbanks T, Yamada K, Warburton D, et al. Dickkopf-1 (DKK1) reveals that fibronectin is a major target of Wnt signaling in branching morphogenesis of the mouse embryonic lung. Dev Biol. 2005;277:316-31 pubmed
    ..DKK1-induced morphogenetic defects can be mimicked by inhibition of FN and overcome by addition of exogenous FN, suggesting an involvement of FN in Wnt-regulated morphogenetic processes. ..
  20. Muranishi Y, Furukawa T. BAC-Dkk3-EGFP transgenic mouse: an in vivo analytical tool for Dkk3 expression. J Biomed Biotechnol. 2012;2012:973140 pubmed publisher
    ..We previously identified Dkk3 to be a molecule predominantly expressed in the mouse embryonic retina...
  21. Das D, Wadhwa N, Kunj N, Sarda K, Pradhan B, Majumdar S. Dickkopf homolog 3 (DKK3) plays a crucial role upstream of WNT/β-CATENIN signaling for Sertoli cell mediated regulation of spermatogenesis. PLoS ONE. 2013;8:e63603 pubmed publisher
    ..Differential display and real time PCR analysis revealed higher expression of a known tumor suppressor, Dickkopf homolog 3 (DKK3), by pubertal monkey Sc as compared to infant Sc...
  22. Zhang Y, Liu Y, Zhu X, Zhang X, Jiang D, Bian Z, et al. Dickkopf-3 attenuates pressure overload-induced cardiac remodelling. Cardiovasc Res. 2014;102:35-45 pubmed publisher
    Dickkopf-3 (DKK3), a secreted protein in the Dickkopf family, is expressed in various tissues, including the heart, and has been shown to play an important role in tissue development...
  23. Zhao G, Zhao S, Liu J, Wu J, He H, Ding X, et al. Cytokeratin 19 promoter directs the expression of Cre recombinase in various epithelia of transgenic mice. Oncotarget. 2017;8:18303-18311 pubmed publisher
    ..Cell specificity of neoplasia is not completely attributable to the cell-specific expression of oncogenes and cell-specific loss of tumor suppressor genes. ..
  24. Darwich R, Li W, Yamak A, Komati H, Andelfinger G, Sun K, et al. KLF13 is a genetic modifier of the Holt-Oram syndrome gene TBX5. Hum Mol Genet. 2017;26:942-954 pubmed publisher
    ..The data also suggest that, in human, KLF13 may be a genetic modifier of the Holt-Oram Syndrome gene TBX5. ..
  25. Vincentz J, Toolan K, Zhang W, Firulli A. Hand factor ablation causes defective left ventricular chamber development and compromised adult cardiac function. PLoS Genet. 2017;13:e1006922 pubmed publisher
    ..Collectively, we conclude that, within a mixed cardiomyocyte population, removal of defective myocardium and replacement with healthy endogenous cardiomyocytes may provide an effective strategy for cardiac repair. ..
  26. Zhang J, Moseley A, Jegga A, Gupta A, Witte D, Sartor M, et al. Neural system-enriched gene expression: relationship to biological pathways and neurological diseases. Physiol Genomics. 2004;18:167-83 pubmed
    ..Together, our data indicate the power of profiling an individual biologic system in a multisystem context to gain insight into the genomic basis of its structure and function. ..
  27. Wong D, Yiu W, Wu H, Li R, Liu Y, Chan K, et al. Downregulation of renal tubular Wnt/β-catenin signaling by Dickkopf-3 induces tubular cell death in proteinuric nephropathy. Cell Death Dis. 2016;7:e2155 pubmed publisher
    ..Taken together, these data suggest that downregulation of tubular β-catenin signaling induced by Dkk-3 has a detrimental role in chronic proteinuria, partially through the increase in apoptosis. ..
  28. Holm P, Mader M, Haubst N, Wizenmann A, Sigvardsson M, Gotz M. Loss- and gain-of-function analyses reveal targets of Pax6 in the developing mouse telencephalon. Mol Cell Neurosci. 2007;34:99-119 pubmed
    ..Most intriguingly, this analysis revealed time- and region-specific differences in Pax6-mediated transcription, explaining the specific function of Pax6 at early and later stages of neurogenesis. ..
  29. Zhu Y, Demidov O, Goh A, Virshup D, Lane D, Bulavin D. Phosphatase WIP1 regulates adult neurogenesis and WNT signaling during aging. J Clin Invest. 2014;124:3263-73 pubmed publisher
    ..We identified the WNT signaling pathway inhibitor DKK3 as a key downstream target of WIP1 and found that expression of DKK3 in the SVZ is restricted to NPCs...
  30. Abarzua F, Sakaguchi M, Tanimoto R, Sonegawa H, Li D, Edamura K, et al. Heat shock proteins play a crucial role in tumor-specific apoptosis by REIC/Dkk-3. Int J Mol Med. 2007;20:37-43 pubmed
  31. Kashiwakura Y, Ochiai K, Watanabe M, Abarzua F, Sakaguchi M, Takaoka M, et al. Down-regulation of inhibition of differentiation-1 via activation of activating transcription factor 3 and Smad regulates REIC/Dickkopf-3-induced apoptosis. Cancer Res. 2008;68:8333-41 pubmed publisher
    ..Thus, gene therapy with REIC/Dkk-3 may be a promising therapeutic tool for MM. ..
  32. Koshiba Takeuchi K, Mori A, Kaynak B, Cebra Thomas J, Sukonnik T, Georges R, et al. Reptilian heart development and the molecular basis of cardiac chamber evolution. Nature. 2009;461:95-8 pubmed publisher
    ..Our findings provide a molecular mechanism for the evolution of the amniote ventricle, and support the concept that altered expression of developmental regulators is a key mechanism of vertebrate evolution. ..
  33. Nie X. Dkk1, -2, and -3 expression in mouse craniofacial development. J Mol Histol. 2005;36:367-72 pubmed
    ..During early craniofacial development, Dkk1 to Dkk3 show developmentally regulated expression in a number of elements...
  34. Pietilä I, Ellwanger K, Railo A, Jokela T, Barrantes I, Shan J, et al. Secreted Wnt antagonist Dickkopf-1 controls kidney papilla development coordinated by Wnt-7b signalling. Dev Biol. 2011;353:50-60 pubmed publisher
    ..Based on the results, we propose that Dkk1 controls the degree of Wnt-7b signalling in the papilla to coordinate kidney organogenesis. ..
  35. Zhang L, Sun C, Jin Y, Gao K, Shi X, Qiu W, et al. Dickkopf 3 (Dkk3) Improves Amyloid-β Pathology, Cognitive Dysfunction, and Cerebral Glucose Metabolism in a Transgenic Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2017;60:733-746 pubmed publisher
    ..b>Dickkopf 3 (Dkk3) is a modulator of the Wnt signaling pathway and is physiologically expressed in the brain...
  36. Chen J, Watanabe M, Huang P, Sakaguchi M, Ochiai K, Nasu Y, et al. REIC/Dkk-3 stable transfection reduces the malignant phenotype of mouse prostate cancer RM9 cells. Int J Mol Med. 2009;24:789-94 pubmed
    ..The result of the proteomics analysis might provide important clues to clarify the anti-cancer molecular mechanism of REIC/Dkk-3 gene transfer. ..
  37. Bluske K, Kawakami Y, Koyano Nakagawa N, Nakagawa Y. Differential activity of Wnt/beta-catenin signaling in the embryonic mouse thalamus. Dev Dyn. 2009;238:3297-309 pubmed publisher
    ..Analysis of mice with enhanced or reduced Shh signal showed that Axin2 expression is similar to controls. These results suggest that differential Wnt signaling may play a role in patterning the thalamus independent of Shh signaling. ..
  38. Nakamura R, Hackam A. Analysis of Dickkopf3 interactions with Wnt signaling receptors. Growth Factors. 2010;28:232-42 pubmed publisher
    ..Recently, we demonstrated that Dickkopf3 (Dkk3) is a pro-survival glycoprotein that positively modulates Wnt signaling...
  39. Papatriantafyllou M, Moldenhauer G, Ludwig J, Tafuri A, Garbi N, Hollmann G, et al. Dickkopf-3, an immune modulator in peripheral CD8 T-cell tolerance. Proc Natl Acad Sci U S A. 2012;109:1631-6 pubmed publisher
    ..Dickkopf-3 (DKK3) was found to be expressed in the tolerant CD8 T cells and to be essential for the observed CD8 T-cell tolerance...
  40. Inoue J, Fujita H, Bando T, Kondo Y, Kumon H, Ohuchi H. Expression analysis of Dickkopf-related protein 3 (Dkk3) suggests its pleiotropic roles for a secretory glycoprotein in adult mouse. J Mol Histol. 2017;48:29-39 pubmed publisher
    Dickkopf-related protein 3 (Dkk3) is the third member of the Dkk gene family and identical to the gene, whose expression was reduced in immortalized cells. Therefore, its another name is reduced expression in immortalized cells...
  41. Geng R, Noda T, Mulvaney J, Lin V, Edge A, Dabdoub A. Comprehensive Expression of Wnt Signaling Pathway Genes during Development and Maturation of the Mouse Cochlea. PLoS ONE. 2016;11:e0148339 pubmed publisher
    ..The data revealed several potential key regulators for further study. ..
  42. Meister M, Tounsi A, Gaffal E, Bald T, Papatriantafyllou M, Ludwig J, et al. Self-Antigen Presentation by Keratinocytes in the Inflamed Adult Skin Modulates T-Cell Auto-Reactivity. J Invest Dermatol. 2015;135:1996-2004 pubmed publisher
    ..Thus, presentation of a neo self-antigen by keratinocytes in the inflamed, adult skin can modulate CD4(+) T-cell auto-aggression at a distal organ. ..
  43. Fame R, Dehay C, Kennedy H, Macklis J. Subtype-Specific Genes that Characterize Subpopulations of Callosal Projection Neurons in Mouse Identify Molecularly Homologous Populations in Macaque Cortex. Cereb Cortex. 2017;27:1817-1830 pubmed publisher
    ..g., Ptn, Nnmt, Cited2, Dkk3), in contrast, the examined genes expressed by superficial layer CPN show more variable levels of conservation (e.g...
  44. Fukusumi Y, Meier F, Götz S, Matheus F, Irmler M, Beckervordersandforth R, et al. Dickkopf 3 Promotes the Differentiation of a Rostrolateral Midbrain Dopaminergic Neuronal Subset In Vivo and from Pluripotent Stem Cells In Vitro in the Mouse. J Neurosci. 2015;35:13385-401 pubmed publisher
    ..b>Dickkopf 3 (DKK3) is a secreted glycoprotein implicated in the modulation of WNT/β-catenin signaling...
  45. Suomalainen M, Thesleff I. Patterns of Wnt pathway activity in the mouse incisor indicate absence of Wnt/beta-catenin signaling in the epithelial stem cells. Dev Dyn. 2010;239:364-72 pubmed publisher
    ..We conclude that epithelial stem cells in the mouse incisors are not regulated directly by Wnt/beta-catenin signaling. ..
  46. Romero D, Kawano Y, Bengoa N, Walker M, Maltry N, Niehrs C, et al. Downregulation of Dickkopf-3 disrupts prostate acinar morphogenesis through TGF-?/Smad signalling. J Cell Sci. 2013;126:1858-67 pubmed publisher
    ..To gain further insight into the function of Dkk-3 in the prostate, we compared the prostates of Dkk3-null mice with those of control littermates...