Summary | Mutation origin | Mutation description | Expression | Phenotypes | Find Mice (IMSR) | References

Symbol:	Notch4tm1Grid
Name:	notch 4; targeted mutation 1, Tom Gridley
MGI ID:	MGI:1929139
Synonyms:	Notch4-, Notch4d1
Gene:	Notch4  Location: Chr17:34783242-34807477 bp, + strand  Genetic Position: Chr17, 18.15 cM
Alliance:	Notch4tm1Grid page

Germline Transmission:	Earliest citation of germline transmission: J:62571
Parent Cell Line:	CJ7 (ES Cell)
Strain of Origin:	129S1/Sv-Oca2+ Tyr+ Kitl+

Allele Type:    Targeted Mutation:    Intragenic deletion   Mutation details: This allele carries a deletion of 1.0 kb of sequence containing exons 21 and 22, which encode part of the extracellular domain of the protein. Subsequent analysis presented in J:212472 revealed that this allele is not null as it overexpresses a truncated transcript encoding most of the extracellular domain of the receptor, including all 29 EGF-like repeats and the Lin12-Notch repeats LNR-A and LNR-B followed by 10 amino acids. The predicted protein lacks the third LNR repeat (LNR-C), heterodimerisation domain, transmembrane domain, and the intracellular domain. Northern blot analysis using a probe upstream of the targeting site containing exons 1 to 5 indicated that Notch4 transcripts are overexpressed 2.6-fold in homozygous and 1.7-fold in heterozygous neonatal lung tissue. Whole-mount immunofluorescence detected strong NOTCH4 reactivity in the developing arteries of P5 homozygous mutant retinas, with heterozygous retinas showing intermediate expression. Importantly, the truncated receptor retains the capacity to inhibit NOTCH1 signaling when expressed in cis, raising the possibility that reported phenotypes may not be due to loss of NOTCH4 function. (J:62571, J:212472)

View phenotypes and curated references for all genotypes (concatenated display).

In Mice Carrying this Mutation:	1 RNA-Seq or microarray experiment(s)
In Structures Affected by this Mutation:	1 anatomical structure(s)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)
Carrying this Mutation:	Mouse Strains: 2 strains available      Cell Lines: 0 lines available
Carrying any Notch4 Mutation:	87 strains or lines available

Original:	J:62571 Krebs LT, et al., Notch signaling is essential for vascular morphogenesis in mice. Genes Dev. 2000 Jun 1;14(11):1343-52
All:	11 reference(s)