Overview

This gene trap mutation abolishes endogenous Fbxw8 gene function while expressing a β-geo reporter fusion protein from the disrupted locus. These Fbxw8^{Gt(pGTOLxf)1Jdec} mice may be useful as a lacZ reporter for Fbxw8 expression or as a knockout model for studying the ubiquitin-proteasome pathway, and early embryonic growth and development.

Donating Investigator

James A. DeCaprio, Dana Farber Cancer Institute

Genetic overview

Genetic Background	Generation

Fbxw8^{Gt(RRT057)Byg}

Allele Type	Gene Symbol	Gene Name
Gene trapped (Reporter, Hypomorph)	Fbxw8	F-box and WD-40 domain protein 8

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Research Applications

Research Tools
Developmental Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The FBXW8 protein is a component of cullin-RING ligase (SKP1-cullin-F box protein complex) that is part of the ubiquitin-proteasome pathway of protein degradation. These mice carry a mutation of the Fbxw8, F-box and WD-40 domain protein 8, gene. Heterozygous mice are viable and fertile. Homozygous mice have a perinatal lethal phenotype with 70% dying soon after birth. Homozygous embryos are viable until late gestation. Gene product (protein) is almost undetectable by Western blot analysis of MEFs from homozygotes. Low levels of gene product (mRNA), 0.8% of levels seen in wildtype controls, are detected in MEFs isolated from homozygotes, as analyzed by real time PCR. At E12.5, homozygotes are smaller in size than controls, and become progressively smaller. By E18.5, the size reduction of homozygous embryos and placentas is significant, 67% of littermate size and 60 to 67% of wildtype placenta size, respectively. Homozygous embryos, aged E18.5, display impaired respiration and quickly become cyanotic. Histological analysis of lungs from homozygous E18.5 embryos reveals diminished alveolar space. Mutant mice exhibit a thin and disorganized placental spongiotrophoblast layer. Homozygotes that survive postnatally are smaller in size than wildtype littermates and exhibit a slower growth rate. Homozygotes, aged 3 months, exhibit smaller organ weight for liver, spleen, kidney, lungs and heart, but have brains similar in size to wildtype mice. Strong β-galactosidase expression is detected in skeletal muscle, developing bone epiphyses, bronchial epithelia of homozygous E14.5 and E18.5 embryos. Weaker β-galactosidase expression is detected in smooth muscle, kidneys, eyes, skin, and brain. β-galactosidase expression is also detected in the placenta. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background.

Development

A "gene trap" targeting vector was used replace endogenous F-box and WD-40 domain protein 8 (Fbxw8) gene function with a β-galactosidase (β-geo) fusion protein in 129P2/OlaHsd-derived embryonic stem (ES) cell line, RRT057. The gene trap contained a β-geo fusion protein inserted into intron 3, 2.6 kb downstream of the exon 3, of the Fbxw8 gene. These ES cells were injected into recipient blastocysts, and chimeric males were bred with C57BL/6 mice. The mice were subsequently backcrossed to C57BL/6 for 10 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Expression Data

Expressed Gene	Bgeo, fusion of beta-galactosidase and neomycin phosphotransferase genes, E. coli
Site of Expression	Strong lacZ expression is detected in skeletal muscle, developing bone epiphyses, bronchial epithelia of homozygous E14.5 and E18.5 embryos. Weaker expression is detected in smooth muscle, kidneys, eyes, skin, and brain.

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Tsutsumi T; Kuwabara H; Arai T; Xiao Y; Decaprio JA. 2008. Disruption of the Fbxw8 gene results in pre- and postnatal growth retardation in mice. Mol Cell Biol 28(2):743-51PubMed: 17998335 MGI: J:130238

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Genetics

Fbxw8^{Gt(RRT057)Byg}

Allele Symbol: Fbxw8^{Gt(RRT057)Byg}

Allele Name	gene trap RRT057, BayGenomics
Allele Type	Gene trapped (Reporter, Hypomorph)
Allele Synonym(s)	Fbxw8^{Gt(pGTOLxf)1Jdec}
Gene Symbol and Name	Fbxw8, F-box and WD-40 domain protein 8
Gene Synonym(s)
Expressed Gene	Bgeo, fusion of beta-galactosidase and neomycin phosphotransferase genes, E. coli
Site of Expression	Strong lacZ expression is detected in skeletal muscle, developing bone epiphyses, bronchial epithelia of homozygous E14.5 and E18.5 embryos. Weaker expression is detected in smooth muscle, kidneys, eyes, skin, and brain.
Strain of Origin	129P2/OlaHsd
Chromosome	5
Molecular Note	A genetrap vector containing a beta-gal reporter and a neomycin selection cassette inserted into intron 3 of the gene locus, 2.6 kb downstream of the exon 3. Western analysis on homozygous embryonic fibroblasts indicated protein expression was at 0.8% of the level in wild-type embryonic fibroblasts. Beta gal expression was detected in numerous tissues of homozygotes including cartilage, skeletal muscle, bronchiolar epithelium, and placenta.
Mutations Made By	Jingwei Cheng, Dana Farber Cancer Institute

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- lacZ Expression
Developmental Biology Research
- Growth Defects
  - Growth Defects (homozygous)
- Perinatal Lethality
  - Homozygous

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Fbxw8^{Gt(RRT057)Byg}/Fbxw8^{Gt(RRT057)Byg}
involves: 129P2/OlaHsd * C57BL/6

embryo phenotype

decreased embryo size
- at E12.5, mice are 83% of wild-type in size

decreased placenta weight
- at mid-gestation, placental weight is 60% to 67% of wild-type

nervous system phenotype

abnormal brain size
- despite all other organs being proportionally reduced according to decreased body size, the brain is the same size as in wild-type mice

respiratory system phenotype

atelectasis
- following recovery at E18.5, alveolar space is reduced compared to in wild-type mice indicating a failure of lungs to inflate

respiratory distress
- recovered E18.5 mice fail to initiate or sustain strong and regular breathing unlike wild-type mice

growth/size/body region phenotype

decreased body weight
- at 1 month of age, surviving mice are 70% of wild-type weight

decreased embryo size
- at E12.5, mice are 83% of wild-type in size

decreased fetal size
- at E18.5, mice are 67% of wild-type in size

slow postnatal weight gain

homeostasis/metabolism phenotype

cyanosis
- in mice recovered at E18.5

mammalian phenotype

skeleton phenotype
- Normal - mice exhibit normal vertebral bodies and femurs

mortality/aging

decreased survivor rate
- while 70% of mice die at birth some survive to weaning

neonatal lethality, incomplete penetrance
- 70% of mice die at birth

References

Tsutsumi T; Kuwabara H; Arai T; Xiao Y; Decaprio JA. 2008. Disruption of the Fbxw8 gene results in pre- and postnatal growth retardation in mice. Mol Cell Biol 28(2):743-51PubMed: 17998335 MGI: J:130238

Additional - Fbxw8^{Gt(RRT057)Byg} related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Fbxw8
- Separated MCA:Fbxw8 MCA
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred with wildtype mice from the colony or with C57BL/6J inbred mice (Stock No. 000664). Homozygous null mice have a perinatal lethal phenotype: 70% of homozygotes (from heterozygous crosses) die soon after birth.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129P2-Fbxw8^{Gt(RRT057)Byg}/JdecJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #018058 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Fbxw8<Gt(RRT057)Byg>

Payment 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. 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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General Terms and Conditions

Questions about Terms of Use

Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Fbxw8Gt(RRT057)Byg

Allele Symbol: Fbxw8Gt(RRT057)Byg

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Fbxw8Gt(RRT057)Byg/Fbxw8Gt(RRT057)Byginvolves: 129P2/OlaHsd * C57BL/6

embryo phenotype

nervous system phenotype

respiratory system phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

mammalian phenotype

mortality/aging

References

Additional - Fbxw8Gt(RRT057)Byg related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Fbxw8^{Gt(RRT057)Byg}

Allele Symbol: Fbxw8^{Gt(RRT057)Byg}

Genotype: Fbxw8^{Gt(RRT057)Byg}/Fbxw8^{Gt(RRT057)Byg}
involves: 129P2/OlaHsd * C57BL/6

Additional - Fbxw8^{Gt(RRT057)Byg} related