These Notch4tm1Grid knock-out mice may be useful in studies of the Notch pathway during development.
Thomas Gridley, Maine Medical Center Research Institute
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted | Notch4 | notch 4 |
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) is detected by RT-PCR analysis of lung and kidney tissue from homozygous adult animals, and in situ hybridization of homozygous embryos. Homozygotes exhibit a slightly elevated systolic blood pressure.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to delete 1.0kb of sequence containing exons 21 and 22, which encodes part of the extracellular domain. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice. Heterozyotes were crossed to generate homozygotes. The mice were bred once to C57BL/6J mice to establish the distribution colony.
Allele Name | targeted mutation 1, Tom Gridley |
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Allele Type | Targeted |
Allele Synonym(s) | Notch4-; Notch4d1 |
Gene Symbol and Name | Notch4, notch 4 |
Gene Synonym(s) | |
Strain of Origin | 129S1/Sv-Oca2+ Tyr+ Kitl+ |
Chromosome | 17 |
Molecular Note | 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. |
Mutations Made By | Thomas Gridley, Maine Medical Center Research Institute |
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Notch4- mouse strain in a publication, please cite the originating article(s) and include JAX stock #010544 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous for Notch4<tm1Grid> |
Frozen Mouse Embryo | B6;129S1-Notch4<tm1Grid>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129S1-Notch4<tm1Grid>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129S1-Notch4<tm1Grid>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6;129S1-Notch4<tm1Grid>/J Frozen Embryo | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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