Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Heterozygote x Heterozygote         (Female x Male)   16-OCT-12 Species laboratory mouse Generation N3+pN1 (15-OCT-12) Generation Definitions   Donating Investigator Iannis Aifantis,   NYU School of Medicine

Description
These Fbw7^f/f mice possess loxP sites flanking exons 5 and 6. These exons encode the F-box domain required for ubiquitination complex assembly. As a ubiquitin ligase, Fbwx7 is involved in targeting the cell cycle regulators c-Myc and Notch1 for proteasomal degradation. Mice that are homozygous for the targeted mutation are viable, fertile and normal in size. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of the floxed allele. This mutant mouse strain may be useful in generating conditional mutations to study regulation of hematopoietic stem cells and tumor suppression.

For example, when crossed to a strain expressing interferon-inducible Cre recombinase (see Stock No. 003556), mice exhibit impaired hematopoietic stem cell self-renewal and differentiation.

Development
A targeting vector was designed to place a loxP site upstream of exon 5 and an FRT-flanked neomycin resistance cassette followed by a loxP site downstream of exon 6. The construct was electroporated into 129/SvEn x C57BL/6-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. Strong chimeras were identified and crossed to C57BL/6 females to verify germline transmission. The F1 generation was PCR screened and crossed to 129S4/SvJaeSor-Gt(ROSA)26Sor^tm1(FLP1)Dym/J (JR#003946) to remove the FRT neo cassette and then further backcrossed to C57BL/6 for at least 3 generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Additional Web Information

Introduction to Cre-lox technology

Use of MICE by companies or for-profit entities requires a license prior to shipping.
Use of MICE by companies or for-profit entities requires a license.

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      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.

Fbxw7^tm1Iaai/Fbxw7^tm1Iaai Tg(Mx1-cre)1Cgn/0

        involves: 129/Sv * C57BL/6 * CBA   (conditional)

• hematopoietic system phenotype
• abnormal T cell differentiation
  • at 2 and 4 weeks after treatment with pIpC, the numbers of early T cell progenitors is decreased compared to in wild-type mice   (MGI Ref ID J:137138)
• • decreased double-negative T cell number
    • following treatment with pIpC, double negative relative and absolute cell numbers are decreased compared to in wild-type mice   (MGI Ref ID J:137138)
    • following treatment with pIpC, DN2 and DN3 cells are almost completely absent   (MGI Ref ID J:137138)
• decreased bone marrow cell number
  • following treatment with pIpC   (MGI Ref ID J:137138)
• decreased hematopoietic stem cell number
  • following treatment with pIpC, the number of LSK (lineage - Sca-1 + c-Kit +) cells is decreased 3- to 5-fold in the bone marrow compared to in wild-type mice   (MGI Ref ID J:137138)
  • following treatment with pIpC, the number of LSKcells is decreased in the blood and spleen compared to in wild-type mice   (MGI Ref ID J:137138)
  • defects in stem cell renewal are cell-autonomous   (MGI Ref ID J:137138)
  • following treatment with pIpC, LSK cell cycling is accelerated with loss of quiescence compared to in wild-type mice   (MGI Ref ID J:137138)
  • following treatment with pIpC, cultured progenitor cells exhibit reduced colony forming capacity and a loss of self-renewal compared to wild-type cells   (MGI Ref ID J:137138)
  • however, the relative abundance of common, megakaryocyte-erythrocyte, and granulocyte-monocyte progenitors and cell cycling of more differentiated progenitor cells than lSK cells are normal   (MGI Ref ID J:137138)
• thymus hypoplasia
  • 4 weeks after treatment with pIpC thymus cellularity is decreased compared to in wild-type mice   (MGI Ref ID J:137138)
  • however, thymus cellularity after 2 weeks of treatment with pIpC is normal   (MGI Ref ID J:137138)
• immune system phenotype
• abnormal T cell differentiation
  • at 2 and 4 weeks after treatment with pIpC, the numbers of early T cell progenitors is decreased compared to in wild-type mice   (MGI Ref ID J:137138)
• • decreased double-negative T cell number
    • following treatment with pIpC, double negative relative and absolute cell numbers are decreased compared to in wild-type mice   (MGI Ref ID J:137138)
    • following treatment with pIpC, DN2 and DN3 cells are almost completely absent   (MGI Ref ID J:137138)
• thymus hypoplasia
  • 4 weeks after treatment with pIpC thymus cellularity is decreased compared to in wild-type mice   (MGI Ref ID J:137138)
  • however, thymus cellularity after 2 weeks of treatment with pIpC is normal   (MGI Ref ID J:137138)
• cellular phenotype
• abnormal T cell differentiation
  • at 2 and 4 weeks after treatment with pIpC, the numbers of early T cell progenitors is decreased compared to in wild-type mice   (MGI Ref ID J:137138)
• • decreased double-negative T cell number
    • following treatment with pIpC, double negative relative and absolute cell numbers are decreased compared to in wild-type mice   (MGI Ref ID J:137138)
    • following treatment with pIpC, DN2 and DN3 cells are almost completely absent   (MGI Ref ID J:137138)

View Research Applications

Research Applications

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

Cancer Research
Tumor Resistance
Tumor Suppressor Genes

Hematological Research
Hematopoietic Defects

Research Tools
Cancer Research
      anti-tumor activity
Cre-lox System
      loxP-flanked Sequences
Genetics Research
      Mutagenesis and Transgenesis: Cre-lox System
Hematological Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Fbxw7tm1Iaai
Allele Name		targeted mutation 1, Iannis Aifantis
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Fbw7flox;
Mutation Made By		Iannis Aifantis,   NYU School of Medicine
Strain of Origin		129/Sv x C57BL/6
Gene Symbol and Name		Fbxw7, F-box and WD-40 domain protein 7
Chromosome		3
Gene Common Name(s)		1110001A17Rik; AGO; CDC4; FBW6; FBW7; FBX30; FBXO30; FBXW6; Fbxo30; RIKEN cDNA 1110001A17 gene; SEL-10; SEL10; f-box only protein 30; hAgo; hCdc4;
Molecular Note		A loxP site was inserted downstream of exon 4 and an frt- and loxP-flanked neo cassette was inserted downstream of exon 6. Germ line, frt-mediated recombination was used to remove the neo cassette leaving exons 5 and 6 floxed. [MGI Ref ID J:137138]

Genotyping

Genotyping Information

Genotyping Protocols

Fbxw7^tm1Iaai, Standard PCR
Generic Cre Melt Curve Analysis, Melt Curve Analysis

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Thompson BJ; Jankovic V; Gao J; Buonamici S; Vest A; Lee JM; Zavadil J; Nimer SD; Aifantis I. 2008. Control of hematopoietic stem cell quiescence by the E3 ubiquitin ligase Fbw7. J Exp Med 205(6):1395-408. [PubMed: 18474632]  [MGI Ref ID J:137138]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	While maintaining a live colony, these mice are bred as homozygotes.
Mating System	Heterozygote x Heterozygote         (Female x Male)   16-OCT-12
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

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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