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| N1::cre mutant mice express a Notch1-Cre fusion protein formed by the insertion of Cre recombinase into the Notch1 locus, replacing the intracellular domain (NICD1).Interaction of N1::cre fusion receptors in vivo with Notch-DSL ligands results in proteolytic cleavage of the transmembrane domain tether and subsequent release of Cre recombinase protein from the plasma membrane. When bred to mice with a loxP-flanked reporter sequence, cell descendants have differential Cre-mediated reporter protein labeling; Notch1 signaling in actively cycling stem/progenitor cells will mark all their descendants producing a "clone", whereas Notch1 activation in transit amplifying or differentiating cells will result in small clones (2-4 cells) or in salt-and-pepper patterns of individually labeled cells. These N1::cre mice make it possible to follow the deccendents of cells that have undergone Notch1 activation, throughout development, self-renewal and malignancy. | |||||||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System +/+ sibling x Heterozygote (Female x Male) 09-JUN-09 Species laboratory mouse Generation N1+ (08-JUN-09) Donating Investigator Raphael Kopan, Washington University in St. Louis Description
While homozygotes die at embryonic day 9.5 (E9.5), mice heterozygous for this N1::cre allele are viable and fertile. Mutant mice express a Notch1-Cre fusion protein formed by the insertion of Cre recombinase into the Notch1 locus replacing the intracellular domain (NICD1). As such, endogenous function of the NICD1 is terminated. Interaction of N1::cre fusion receptors in vivo with Notch-DSL (-Delta, Serrate and Lag-2) ligands results in proteolytic cleavage of the transmembrane domain tether and subsequent release of Cre recombinase protein from the plasma membrane. When bred to mice with a loxP-flanked reporter sequence, cell descendants have differential Cre-mediated reporter protein labeling; Notch1 signaling in actively cycling stem/progenitor cells will mark all their descendants producing a "clone", whereas Notch1 activation in transit amplifying or differentiating cells will result in small clones (2-4 cells) or in salt-and-pepper patterns of individually labeled cells. These N1::cre mice are models of in vivo Notch1 Intramembrane Proteolysis (N1IP-CRE); allowing studies to monitor descendants of cells throughout development, self-renewal and malignancy.Development
The N1::cre targeting construct was designed to replace the Notch1 (N1) intracellular domain (exons 29-34) with a Cre recombinase sequence (without its ATG start site) and nuclear localization signal, followed immediately downstream by a C-terminal 6xMyc epitope tag and SV40 polyadenylation sequence. A frt-flanked Neo cassette was also inserted downstream. The construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts to generate chimeric mice. Mice that transmitted the N1::cre allele through the germ line were crossed with Flp-deleter mice (on a mixed B6;SJL genetic background, see Stock No. 003800) to remove the selection cassette. After this, N1::cre mice were bred to remove the Flp-deleter transgene. At some point, N1::cre mice were also bred with Gt(ROSA)26Sortm1Sor mutant mice (on a mixed CD1, C57BL/6, and 129S genetic background). N1::cre mice on a mixed CD1 and C57BL/6 (and 129S) genetic background (still harboring Gt(ROSA)26Sortm1Sor) were sent to The Jackson Laboratory. Upon arrival, mutant mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to remove the unwanted Gt(ROSA)26Sor mutation and to establish this N1::cre colony.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Notch1
002797 B6.129-Notch1tm1Con/J 007181 B6.129X1-Notch1tm2Rko/GridJ 002445 STOCK Notch1tm1Con/J 006951 STOCK Notch1tm2Rko/GridJ View Strains carrying other alleles of Notch1 (4 strains)
Additional Web Information
Introduction to Cre-lox technology
Phenotype
Phenotype Information
assigned by genotype
Notch1tm3(cre)Rko/Notch1tm3(cre)Rko
involves: 129X1/SvJ * C57BL/6J * SJL
- lethality-prenatal/perinatal
- embryonic lethality during organogenesis (MGI Ref ID J:119910)
- homozygous embryos die at E9.5
This mouse can be used to support research in many areas including:
Notch1 relatedCell Biology Research
Genes Regulating Growth and Proliferation
Signal Transduction
Developmental Biology Research
Embryonic Lethality (Homozygous)
Research Tools
Cre-lox System
Cre Recombinase Expression
Developmental Biology Research
Cre-lox System
Genetics Research
Mutagenesis and Transgenesis: Cre-lox System
Tissue/Cell Markers: Cre-lox System
Tissue/Cell Markers: multiple
Developmental Biology Research
Embryonic Lethality (Homozygous)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Notch1tm3(cre)Rko | ||
|---|---|---|---|
| Allele Name | targeted mutation 3, Raphael Kopan | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | N1::cre; N1::cretg; | ||
| Mutation Made By | Raphael Kopan, Washington University in St. Louis | ||
| Strain of Origin | 129X1/SvJ | ||
| ES Cell Line Name | RW-4 | ||
| ES Cell Line Strain | 129X1/SvJ | ||
| Gene Symbol and Name | Notch1, Notch gene homolog 1 (Drosophila) | ||
| Chromosome | 2 | ||
| Gene Common Name(s) | 9930111A19Rik; Mis6; Motch A; NOTCH; RIKEN cDNA 9930111A19 gene; TAN1; Tan1; hN1; lin-12; translocation-associated Notch; | ||
| Driver Note | Notch1 | ||
| Molecular Note | The intracellular domain was replaced with cre recombinase. [MGI Ref ID J:119910] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Gt(ROSA)26Sortm1sor STD, Standard PCR
Notch1tm3(cre)Rko, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Vooijs M; Ong CT; Hadland B; Huppert S; Liu Z; Korving J; van den Born M; Stappenbeck T; Wu Y; Clevers H; Kopan R. 2007. Mapping the consequence of Notch1 proteolysis in vivo with NIP-CRE. Development 134(3):535-44. [PubMed: 17215306] [MGI Ref ID J:119910]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous mice are bred to wildtype siblings. Homozygotes die in utero. Mating System +/+ sibling x Heterozygote (Female x Male) 09-JUN-09 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
This strain is currently Under Development for Production.
To register your interest in this strain go to the Strain Interest Form.
Estimated Available for Sale Date: 23-NOV-09
Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.
View All Strains Under Development and On Hold
Supply Details
| Standard Supply | Under Development for Distribution Colony |
|---|---|
| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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.Ordering and Purchasing Information
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