In this ROSA NOTCH3-455 knockin strain, the human NOTCH3 gene is altered by the CADASIL-associated C455R 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
Homozygotes: Homozygous ROSA NOTCH3-455 mice are viable, fertile, with the CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)-associated C445R 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 at was inserted into the GT(ROSA)26Sor locus. The CADASIL mutation is an amino acid substitution from cysteine to arginine at amino acid 455 (C455R). The construct was introduced into 129S6/SvEvTac -derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting "455" chimeric animals were crossed to 129S2/SvEv mice. The mice were crossed to 129S2/SvEv for an unknown number of generations. Upon arrival, mice were bred to 129S1/SvImJ for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 2, Spyros Artavanis-Tsakonas|
|Allele Type||Targeted (Conditional ready (e.g. floxed), Humanized sequence, Inserted expressed sequence, Reporter)|
|Gene Symbol and Name||Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano|
|Gene Synonym(s)||AV258896; Gtrgeo26; Gtrgeo26; Gtrosa26; Gtrosa26; R26; ROSA26; SETD5-AS1; beta geo; expressed sequence AV258896; gene trap ROSA 26; gene trap ROSA b-geo 26|
|Strain of Origin||129S6/SvEvTac|
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