Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N5 (01-MAY-08)   Donating Investigator Raphael Kopan,   Washington Univeristy

Description
Mice homozygous for this "floxed" Notch1 allele (fN1) are viable and fertile. These mice possess loxP sites on either side of exon 1 of the targeted gene. When bred to mice with a Cre recombinase gene, exon 1 of the targeted gene is deleted in the cre expressing tissue(s). These conditional knockout mice may be useful in generating tissue-specific mutants for studying the development of a wide range of tissues: for example, when crossed to a strain expressing Cre recombinase primarily in the nervous system (see Stock No. 003771), this mutant strain may be useful in studies of apoptosis in neural development.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting construct was designed to place a loxP-flanked PGK-neo cassette upstream of exon 1 of the targeted gene, as well as a single loxP site in intron 1. The construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a Cre recombinase vector to remove the selection cassette. The resulting ES cells harboring the loxP-flanked exon 1 were injected into blastocysts to generate chimeric mice. Mutant mice were then sent to Dr. Thomas Gridley (The Jackson Laboratory) in 2003 on an unspecified mixed genetic background. These mice were supplied to The Jackson Laboratory Repository (as Stock No. 006951) in 2007. After this, some mice were backcrossed to C57BL/6J for at least 5 generations to generate this congenic strain (Stock No. 007181).

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Notch1^tm2Rko allele

006951

STOCK Notch1tm2Rko/GridJ

View Strains carrying   Notch1^tm2Rko     (1 strain)

Strains carrying other alleles of Notch1

002797	B6.129-Notch1tm1Con/J
002445	STOCK Notch1tm1Con/J

View Strains carrying other alleles of Notch1     (2 strains)

Additional Web Information

Congenic Nomenclature
Cre-lox Systems

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Notch1^tm2Rko/Notch1^tm2Rko Tg(Nes-cre)1Kln/0

        involves: 129X1/SvJ * C57BL/6J * SJL   (conditional)

• cellular phenotype
• abnormal apoptosis (MGI Ref ID J:90392)
  • at E10 the total number of apoptotic cells and relative percentage of apoptotic cells to progenitor cells in the forebrain-midbrain junction is significantly reduced compared to littermate controls
• nervous system phenotype
• increased neuron number (MGI Ref ID J:90392)
  • the number of postmitotic neurons is increased in the telencephalon at E11.5 - 12.5 compared to littermate controls

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cell Biology Research
Genes Regulating Growth and Proliferation
Signal Transduction

Developmental Biology Research
Growth Defects

Research Tools
Cell Biology Research
Cre-lox System (loxP-flanked Sequences)
Developmental Biology Research (Cre-lox System)

Notch1 related

Developmental Biology Research
Embryonic Lethality (Homozygous)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Notch1tm2Rko
Allele Name		targeted mutation 2, Raphael Kopan
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Notch1flox; Notch1tm1Shn; fN1;
Mutation Made By		Raphael Kopan,   Washington Univeristy
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; NOTCH; RIKEN cDNA 9930111A19 gene; TAN1; Tan1; hN1; lin-12; translocation-associated Notch;
Molecular Note		LoxP were inserted flanking the first coding exon of the gene. An adjacent loxP flanked neomycin cassette was removed by Cre-mediated recombination in ES cells prior to production of chimeric animals. [MGI Ref ID J:90392]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Yang X; Klein R; Tian X; Cheng HT; Kopan R; Shen J. 2004. Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway. Dev Biol 269(1):81-94. [PubMed: 15081359]  [MGI Ref ID J:90392]

Additional References

Notch1^tm2Rko related

Bai S; Kopan R; Zou W; Hilton MJ; Ong CT; Long F; Ross FP; Teitelbaum SL. 2008. NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells. J Biol Chem 283(10):6509-18. [PubMed: 18156632]  [MGI Ref ID J:133664]

Del Barrio MG; Taveira-Marques R; Muroyama Y; Yuk DI; Li S; Wines-Samuelson M; Shen J; Smith HK; Xiang M; Rowitch D; Richardson WD. 2007. A regulatory network involving Foxn4, Mash1 and delta-like 4/Notch1 generates V2a and V2b spinal interneurons from a common progenitor pool. Development 134(19):3427-36. [PubMed: 17728344]  [MGI Ref ID J:128001]

Demehri S; Liu Z; Lee J; Lin MH; Crosby SD; Roberts CJ; Grigsby PW; Miner JH; Farr AG; Kopan R. 2008. Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity. PLoS Biol 6(5):e123. [PubMed: 18507503]  [MGI Ref ID J:139386]

Huppert SS; Ilagan MX; De Strooper B; Kopan R. 2005. Analysis of Notch Function in Presomitic Mesoderm Suggests a gamma-Secretase-Independent Role for Presenilins in Somite Differentiation. Dev Cell 8(5):677-88. [PubMed: 15866159]  [MGI Ref ID J:98438]

Kiernan AE; Cordes R; Kopan R; Gossler A; Gridley T. 2005. The Notch ligands DLL1 and JAG2 act synergistically to regulate hair cell development in the mammalian inner ear. Development 132(19):4353-62. [PubMed: 16141228]  [MGI Ref ID J:132241]

Lee J; Basak JM; Demehri S; Kopan R. 2007. Bi-compartmental communication contributes to the opposite proliferative behavior of Notch1-deficient hair follicle and epidermal keratinocytes. Development 134(15):2795-806. [PubMed: 17611229]  [MGI Ref ID J:124114]

Pan Y; Lin MH; Tian X; Cheng HT; Gridley T; Shen J; Kopan R. 2004. gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis. Dev Cell 7(5):731-43. [PubMed: 15525534]  [MGI Ref ID J:94517]

Pan Y; Liu Z; Shen J; Kopan R. 2005. Notch1 and 2 cooperate in limb ectoderm to receive an early Jagged2 signal regulating interdigital apoptosis. Dev Biol 286(2):472-82. [PubMed: 16169548]  [MGI Ref ID J:103603]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	Mutant mice were bred to C57BL/6J mice to generate this congenic strain. When maintaining the live congenic colony, mice may be bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
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.

General Terms and Conditions

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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.

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