| First Author | Ge C | Year | 2008 |
| Journal | Proc Natl Acad Sci U S A | Volume | 105 |
| Issue | 5 | Pages | 1539-44 |
| PubMed ID | 18227520 | Mgi Jnum | J:131563 |
| Mgi Id | MGI:3773966 | Doi | 10.1073/pnas.0702846105 |
| Citation | Ge C, et al. (2008) The O-fucose glycan in the ligand-binding domain of Notch1 regulates embryogenesis and T cell development. Proc Natl Acad Sci U S A 105(5):1539-44 |
| abstractText | Mechanisms by which the extracellular domain of Notch1 controls Notch1 signaling are not well defined. Here, we show that the O-fucose glycan in the Notch1 ligand-binding domain regulates the strength of Notch1 signaling during embryogenesis, postweaning growth, and T cell development in the mouse. Heterozygotes carrying a Notch1(12f) allele and an inactive Notch1 allele die at approximately embryonic day (E)12 with a typical Notch1 null phenotype. Homozygous Notch1(12f/12f) mice are viable and fertile but grow somewhat more slowly than littermates after weaning. Notch1(12f/12f) thymocytes bind less Delta1 and exhibit reduced Notch1 signaling. The number of double-positive (DP) and single-positive (SP) T cells are decreased in Notch1(12f/12f) thymus, and DP T cells are more apoptotic. By contrast, proportionately more SP cells have matured, and SP-to-DP ratios are increased in mutant thymus. Thus, the O-fucose glycan in EGF12 of mouse Notch1 is required for optimal Notch1 signaling and T cell development in mammals. |
