In this ROSA NOTCH3-1031 knockin strain, the human NOTCH3 gene is altered by the CADASIL-associated R1031C mutation and expression is blocked by an upstream loxP-flanked STOP sequence. Cre-mediated excision results in expression of the mutated NOTCH3 and GFP targeted to the nucleus. Expression in vascular smooth muscle cells is characterized by cell degeneration and the presence of granular osmiophilic deposits. These mice allow inducible expression of a human mutation associated with ischemic stroke.
Spyros Artavanis-Tsakonas, Harvard Medical School
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Conditional ready (e.g. floxed), Reporter, Inserted expressed sequence, Humanized sequence) | Gt(ROSA)26Sor | gene trap ROSA 26, Philippe Soriano |
Homozygotes: Homozygous ROSA NOTCH3-1031 mice are viable, fertile, with the CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)-associated R1031C mutation inserted into the Gt(ROSA)26Sor locus. Expression of the mutated human NOTCH3 is blocked by an upstream loxP-flanked STOP sequence. When bred to cre expressing mice, the STOP sequence is deleted in the tissues of offspring where Cre recombinase is present, resulting in mutated human NOTCH3 expression and the parallel expression of enhanced green fluorescent protein (GFP) targeted to the nucleus. Expression in vascular smooth muscle cells is characterized by cell degeneration and the presence of granular osmiophilic deposits. These mice allow inducible expression of a human mutation associated with ischemic stroke.
Heterozygote: Not evaluated
A targeting vector was designed with a splice acceptor site, a loxP-flanked PGK neomycin cassette, a human NOTCH3 cDNA encoding a CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)-associated mutation and an IRES-nuclear EGFP sequence was inserted into the GT(ROSA)26Sor locus. The CADASIL mutation is an amino acid substitution from arginine to cysteine at amino acid 1031 (R1031C). The construct was introduced into 129S6/SvEvTac-derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting "1031" chimeric animals were crossed to 129S2/SvEv mice. The mice were crossed to 129S2/SvEv for an unknown number of generations and at some point to C57BL/6 mice. Upon arrival, mice were bred to 129S1/SvImJ for at least 1 generation to establish the colony.
Expressed Gene | NOTCH3, notch 3, human |
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Expressed Gene | GFP, Green Fluorescent Protein, |
Site of Expression | EGFP and human NOTCH3 will be expressed in cells where promoters driving Cre recombinase are expressed. |
Allele Name | targeted mutation 3, Spyros Artavanis-Tsakonas |
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Allele Type | Targeted (Conditional ready (e.g. floxed), Reporter, Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | Gt(ROSA)26Sortm1(NOTCH3*R1031C)Sat; NOTCH3R1031C |
Gene Symbol and Name | Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano |
Gene Synonym(s) | |
Expressed Gene | NOTCH3, notch 3, human |
Expressed Gene | GFP, Green Fluorescent Protein, |
Site of Expression | EGFP and human NOTCH3 will be expressed in cells where promoters driving Cre recombinase are expressed. |
Strain of Origin | 129S6/SvEvTac |
Chromosome | 6 |
Molecular Note | A targeting vector containing a splice acceptor site, a floxed PGK neomycin cassette, a human NOTCH3 cDNA with an R1031C mutation and an IRES-nuclear GFP sequence was inserted via homologous recombination. |
While maintaining a live colony, these mice are bred as homozygotes.
When using the B6;129S-Gt(ROSA)26Sortm1(NOTCH3*R1031C)Sat/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32999 in your Materials and Methods section.
Facility Barrier Level Descriptions
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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