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Gene Review

Notch2  -  notch 2

Mus musculus

Synonyms: AI853703, Motch B, N2, Neurogenic locus notch homolog protein 2, Notch 2
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Disease relevance of Notch2

  • Using gene targeting procedures, we disrupted the mouse Notch2 gene by replacing all but one of the ankyrin repeat sequences in the cytoplasmic domain with the E. coli (beta)-galactosidase gene [1].
  • In the present work we present evidence that gamma-radiation-induced thymic lymphomas in (C57BL/6 J x BALB/c) F1 hybrid mice often exhibit increased levels of Notch1 expression, but, contrary to what was expected, they also exhibit a clearly reduced Notch2 mRNA expression, suggesting a cooperative antagonism of these genes [2].
  • Deletion of Notch1 and/or Notch2 in melanoblasts did not induce a congenital defect [3].
  • Disruption of pulmonary Notch-2 signaling continued in newborn low-Foxf1(+/-) mice, which died of lung hemorrhage and failed to compensate for Foxf1 haploinsufficiency [4].
  • We demonstrate that different lots of a baculovirus-derived recombinant N2 protein, in the absence of other influenza virus proteins, can induce neuraminidase-specific antibodies, reduce the replication of both homologous and heterovariant virus in mice, and suppress disease, as it is manifested by total body weight loss [5].

High impact information on Notch2


Biological context of Notch2

  • We report that expression of Notch signaling genes is spatially and temporally regulated in pituitary embryogenesis and implicate Notch2 in the differentiation of several cell lineages [10].
  • We also show a marked downregulation in the expression of Notch2, Jagged1, Hes1, mSfrp1, and mFrz7 in cerebella of developing mice with reduced Hh signaling, suggesting that Hh signaling regulates the expression of these genes [11].
  • Cells from Notch2 mutant mice attach and grow normally in culture, demonstrating that Notch2 deficiency does not interfere with cell proliferation and that expression of the Notch2-(beta)-gal fusion protein is not toxic per se [1].
  • Notch2 homozygous mutant mice die prior to embryonic day 11.5, whereas heterozygotes show no apparent abnormalities and are fully viable [1].
  • Although studies have shown that the Notch2 family member is critical for embryonic development, little is known concerning its role in hematopoiesis [12].

Anatomical context of Notch2


Associations of Notch2 with chemical compounds


Physical interactions of Notch2


Regulatory relationships of Notch2


Other interactions of Notch2

  • All Notch signaling pathway receptors and ligands tested were expressed in the rhombic lip at embryonic date 14, with highest levels of Notch2 and Jag1 [22].
  • Notch1, Notch2 and Notch3 were immunohistochemically detected in non-neuroendocrine cells [23].
  • Transgenic overexpression of Prop1 is not sufficient for enhancement of endogenous Notch2 expression, indicating that there are multiple inputs into this pathway [10].
  • Hypertrophic chondrocytes within the growth plate also expressed Notch 2 and 4, Delta and Jagged 2 (which was also expressed in prehypertrophs) [24].
  • In contrast, in newborn high-Foxf1(+/-) lungs, Notch-2 signaling was restored to the level found in wild-type mice, which was associated with normal microvascular formation and survival [4].

Analytical, diagnostic and therapeutic context of Notch2


  1. Mutation in ankyrin repeats of the mouse Notch2 gene induces early embryonic lethality. Hamada, Y., Kadokawa, Y., Okabe, M., Ikawa, M., Coleman, J.R., Tsujimoto, Y. Development (1999) [Pubmed]
  2. Defective expression of Notch1 and Notch2 in connection to alterations of c-Myc and Ikaros in gamma-radiation-induced mouse thymic lymphomas. López-Nieva, P., Santos, J., Fernández-Piqueras, J. Carcinogenesis (2004) [Pubmed]
  3. Notch1 and Notch2 receptors influence progressive hair graying in a dose-dependent manner. Schouwey, K., Delmas, V., Larue, L., Zimber-Strobl, U., Strobl, L.J., Radtke, F., Beermann, F. Dev. Dyn. (2007) [Pubmed]
  4. Foxf1 haploinsufficiency reduces Notch-2 signaling during mouse lung development. Kalinichenko, V.V., Gusarova, G.A., Kim, I.M., Shin, B., Yoder, H.M., Clark, J., Sapozhnikov, A.M., Whitsett, J.A., Costa, R.H. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  5. Protection of mice with recombinant influenza virus neuraminidase. Kilbourne, E.D., Pokorny, B.A., Johansson, B., Brett, I., Milev, Y., Matthews, J.T. J. Infect. Dis. (2004) [Pubmed]
  6. Notch1 is essential for postimplantation development in mice. Swiatek, P.J., Lindsell, C.E., del Amo, F.F., Weinmaster, G., Gridley, T. Genes Dev. (1994) [Pubmed]
  7. Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development. Saito, T., Chiba, S., Ichikawa, M., Kunisato, A., Asai, T., Shimizu, K., Yamaguchi, T., Yamamoto, G., Seo, S., Kumano, K., Nakagami-Yamaguchi, E., Hamada, Y., Aizawa, S., Hirai, H. Immunity (2003) [Pubmed]
  8. Notch1 but not Notch2 is essential for generating hematopoietic stem cells from endothelial cells. Kumano, K., Chiba, S., Kunisato, A., Sata, M., Saito, T., Nakagami-Yamaguchi, E., Yamaguchi, T., Masuda, S., Shimizu, K., Takahashi, T., Ogawa, S., Hamada, Y., Hirai, H. Immunity (2003) [Pubmed]
  9. The role of notch signaling in the development of intrahepatic bile ducts. Kodama, Y., Hijikata, M., Kageyama, R., Shimotohno, K., Chiba, T. Gastroenterology (2004) [Pubmed]
  10. Developmental regulation of Notch signaling genes in the embryonic pituitary: Prop1 deficiency affects Notch2 expression. Raetzman, L.T., Ross, S.A., Cook, S., Dunwoodie, S.L., Camper, S.A., Thomas, P.Q. Dev. Biol. (2004) [Pubmed]
  11. Expression of Notch and Wnt pathway components and activation of Notch signaling in medulloblastomas from heterozygous patched mice. Dakubo, G.D., Mazerolle, C.J., Wallace, V.A. J. Neurooncol. (2006) [Pubmed]
  12. Activated Notch2 potentiates CD8 lineage maturation and promotes the selective development of B1 B cells. Witt, C.M., Hurez, V., Swindle, C.S., Hamada, Y., Klug, C.A. Mol. Cell. Biol. (2003) [Pubmed]
  13. Notch-associated gene expression in embryonic and adult taste papillae and taste buds suggests a role in taste cell lineage decisions. Seta, Y., Seta, C., Barlow, L.A. J. Comp. Neurol. (2003) [Pubmed]
  14. Characterization of Notch receptor expression in the developing mammalian heart and liver. Loomes, K.M., Taichman, D.B., Glover, C.L., Williams, P.T., Markowitz, J.E., Piccoli, D.A., Baldwin, H.S., Oakey, R.J. Am. J. Med. Genet. (2002) [Pubmed]
  15. Testosterone influenced the expression of Notch1, Notch2 and Jagged1 induced by lipopolysaccharide in macrophages. Guo, D., Zhang, H., Liu, L., Wang, L., Cheng, Y., Qiao, Z. Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie. (2004) [Pubmed]
  16. Notch pathway genes are expressed in mammalian ovarian follicles. Johnson, J., Espinoza, T., McGaughey, R.W., Rawls, A., Wilson-Rawls, J. Mech. Dev. (2001) [Pubmed]
  17. Notch2 expression negatively correlates with glial differentiation in the postnatal mouse brain. Tanaka, M., Kadokawa, Y., Hamada, Y., Marunouchi, T. J. Neurobiol. (1999) [Pubmed]
  18. Long-lasting induction of Notch2 in the hippocampus of kainate-treated adult mice. Toninelli, G.F., Bernardi, C., Quarto, M., Lozza, G., Memo, M., Grilli, M. Neuroreport (2003) [Pubmed]
  19. Notch signaling is necessary but not sufficient for differentiation of dendritic cells. Cheng, P., Nefedova, Y., Miele, L., Osborne, B.A., Gabrilovich, D. Blood (2003) [Pubmed]
  20. Notch signaling controls hepatoblast differentiation by altering the expression of liver-enriched transcription factors. Tanimizu, N., Miyajima, A. J. Cell. Sci. (2004) [Pubmed]
  21. Complementary and combinatorial patterns of Notch gene family expression during early mouse development. Williams, R., Lendahl, U., Lardelli, M. Mech. Dev. (1995) [Pubmed]
  22. Math1 controls cerebellar granule cell differentiation by regulating multiple components of the Notch signaling pathway. Gazit, R., Krizhanovsky, V., Ben-Arie, N. Development (2004) [Pubmed]
  23. Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epithelium. Ito, T., Udaka, N., Yazawa, T., Okudela, K., Hayashi, H., Sudo, T., Guillemot, F., Kageyama, R., Kitamura, H. Development (2000) [Pubmed]
  24. The distribution of Notch receptors and their ligands during articular cartilage development. Hayes, A.J., Dowthwaite, G.P., Webster, S.V., Archer, C.W. J. Anat. (2003) [Pubmed]
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