A modifier in the 129S2/SvPasCrl genome is responsible for the viability of Notch1[12f/12f] mice.

ABSTRACT:

Background

Mouse 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^tm2Pst). Surprisingly, homozygous Notch1[12f/12f] mutants on a mixed background were viable and fertile.

Results

We now report that after backcrossing to C57BL/6 J mice for 11-15

SUBMITTER: Varshney S 

PROVIDER: S-EPMC6781419 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature