ArticleBMC developmental biology2019
A modifier in the 129S2/SvPasCrl genome is responsible for the viability of Notch1[12f/12f] mice.
Article in BMC developmental biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Genetics of glycosylation in mammalian development and disease.Nature reviews. Genetics · 2024Review
- Analysis of endogenous NOTCH1 from POFUT1 S162L patient fibroblasts reveals the importance of the O-fucose modification on EGF12 in human development.Glycobiology · 2024Article
- In vivo evidence for GDP-fucose transport in the absence of transporter SLC35C1 and putative transporter SLC35C2.The Journal of biological chemistry · 2023Article
- EOGT enables residual Notch signaling in mouse intestinal cells lacking POFUT1.Scientific reports · 2023Article
- Article
- A case of complex balanced chromosomal translocations associated with adverse pregnancy outcomes.Molecular cytogenetics · 2022Article
- Glycans that regulate Notch signaling in the intestine.Biochemical Society transactions · 2022Review
- Regulation of myeloid and lymphoid cell development by O-glycans on Notch.Frontiers in molecular biosciences · 2022Review
- Modulation of the NOTCH1 Pathway by LUNATIC FRINGE Is Dominant over That of MANIC or RADICAL FRINGE.Molecules (Basel, Switzerland) · 2021Article
- Current Views on the Roles ofBiomolecules · 2021Review
- Multifaceted regulation of Notch signaling by glycosylation.Glycobiology · 2021Review
- Canonical Notch ligands and Fringes have distinct effects on NOTCH1 and NOTCH2.The Journal of biological chemistry · 2020Article
- Expression, purification, and glycosylation of epidermal growth factor-like repeat 27 from mouse NOTCH1.Protein expression and purification · 2020Article
- Transgenic Rescue of Spermatogenesis in Males WithFrontiers in cell and developmental biology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundMouse NOTCH1 carries a highly conserved O-fucose glycan at Thr466 in epidermal growth factor-like repeat 12 (EGF12) of the extracellular domain. O-Fucose at this site has been shown by X-ray crystallography to be recognized by both DLL4 and JAG1 Notch ligands. We previously showed that a Notch1 Thr466Ala mutant exhibits very little ligand-induced NOTCH1 signaling in a reporter assay, whereas a Thr466Ser mutation enables the transfer of O-fucose and reverts the NOTCH1 signaling defect. We subsequently generated a mutant mouse with the Thr466Ala mutation termed Notch1[12f](Notch1
resultsWe now report that after backcrossing to C57BL/6 J mice for 11-15 generations, few homozygous Notch1[12f/12f] embryos were born. Timed mating showed that embryonic lethality occurred by embryonic day (E) ~E11.5, somewhat delayed compared to mice lacking Notch1 or Pofut1 (the O-fucosyltransferase that adds O-fucose to Notch receptors), which die at ~E9.5. The phenotype of C57BL/6 J Notch1[12f/12f] embryos was milder than mutants affected by loss of a canonical Notch pathway member, but disorganized vasculogenesis in the yolk sac, delayed somitogenesis and development were characteristic. In situ hybridization of Notch target genes Uncx4.1 and Dll3 or western blot analysis of NOTCH1 cleavage did not reveal significant differences at E9.5. However, qRT-PCR of head cDNA showed increased expression of Dll3, Uncx4.1 and Notch1 in E9.5 Notch1[12f/12f] embryos. Sequencing of cDNA from Notch1[12f/12f] embryo heads and Southern analysis showed that the Notch1[12f] locus was intact following backcrossing. We therefore looked for evidence of modifying gene(s) by crossing C57BL/6 J Notch1 [12f/+] mice to 129S2/SvPasCrl mice. Intercrosses of the F1 progeny gave viable F2 Notch1[12f/12f] mice.
conclusionWe conclude that the 129S2/SvPasCrl genome contains a dominant modifying gene that rescues the functions of NOTCH1[12f] in signaling. Identification of the modifying gene has the potential to illuminate novel factor(s) that promote Notch signaling when an O-fucose glycan is absent from EGF12 of NOTCH1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.