Overview

Also Known As:Fadd Knock-out

This Fadd knockout strain may be useful in studies of apoptosis and immune response involving interferon signaling.

Donating Investigator

Dr. Tak Mak, University Health Network / University of Toronto

Genetic overview

Genetic Background	Generation

Fadd^tm1Mak

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Fadd	Fas (TNFRSF6)-associated via death domain

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Research Applications

Developmental Biology Research
Apoptosis Research
Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The targeted Fadd gene encodes an apoptosis adaptor protein with a C-terminal death domain that is involved in signaling between death receptors and caspases, as well as early T cell development.
Mutations in this gene have been associated with fadd-related immunodeficiency.
These knock-out mice carry an allele in which the entire coding region of the Fadd gene has been replaced by a PGK-Neo cassette in opposite orientation. No gene product (protein) is detected by Western blot analysis of total protein lysates from homozygotes.
Mice that are heterozygous for this allele are viable and fertile. Homozygotes exhibit an embryonic lethal phenotype, failing to survive past embryonic day E12.5. Most homozygous embryos are smaller in size than controls, and exhibit thin ventricular myocardium and under-developed inner trabeculation by E10.5. By E11.5, approximately 50% homozygous embryos are hemorrhagic. Primary embryonic fibroblasts isolated from homozygotes show impaired TNF-induced endosomal acid sphingomyelinase activation, and are not induced into apoptosis by FAS (CD95), TNFRSF1A (TNF-R55), and TNFRSF25 (DR3). During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background.

Development

A targeting vector containing a PGK-Neo (in reverse orientation) was used to disrupt the entire coding region of the Fadd gene (2 exons). The construct was electroporated into 129P2/OlaHsd derived E14K embryonic stem (ES) cells.
Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric males animals were bred to C57BL/6J females.
The mice were backcrossed to C57BL/6 for 8 generations by the donating lab (see SNP note below). During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background.
Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Three of the 43 markers throughout the genome were segregating, suggesting an incomplete backcross. Also, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Yeh WC; Pompa JL; McCurrach ME; Shu HB; Elia AJ; Shahinian A ; Ng M ; Wakeham A ; Khoo W ; Mitchell K ; El-Deiry WS ; Lowe SW ; Goeddel DV ; Mak TW. 1998. FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis. Science 279(5358):1954-8PubMed: 9506948 MGI: J:46527

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Genetics

Fadd^tm1Mak

Allele Symbol: Fadd^tm1Mak

Allele Name	targeted mutation 1, Tak W Mak
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Fadd, Fas (TNFRSF6)-associated via death domain
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	7
General Note	Authors in J:46527 state that injection of mutant ES cells into Gt(ROSA)26Sor E3.5 blastocysts (J:79478) resulting in high percentage chimeric embryos with a high contribution of mutant cells to the heart reproduce the phenotype of homozygous mutant embryos derived from heterozygous breedings. In contrast, chimeric embryos with a low contribution from the mutant ES cells display a normal phenotype at E11.5.
Molecular Note	A neomycin selection cassette replaced a genomic fragment containing the entire coding region of the gene. Western blot analysis on lysates derived from homozygous mice confirmed that no detectable protein was expressed from this allele.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Developmental Biology Research
- Growth Defects
  - Growth Defects (homozygous)
- Embryonic Lethality (Homozygous)
Apoptosis Research
Research Tools
- Apoptosis Research

Mammalian Phenotype Terms by Genotype

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

Genotype: Fadd^tm1Mak/Fadd^tm1Mak
either: (involves: 129P2/OlaHsd * C57BL/6J) or (involves: 129P2/OlaHsd * CD-1)

growth/size/body region phenotype

decreased embryo size
- at E11.5, ~80% of homozygotes are smaller in size relative to wild-type embryos

embryonic growth retardation
- at E11.5, ~80% of homozygotes appear underdeveloped and growth retarded relative to wild-type embryos, despite normal placental development and absence of excessive apoptosis or reduced cellular proliferation

mortality/aging

embryonic lethality during organogenesis, complete penetrance
- homozygotes are present at the expected Mendelian frequency (25%) up to E9.5
- however, viable mutant embryos are obtained at a reduced frequency from E10.5 (18.8%) to E11.5 (4.1%), until all are dead by E12.5 probably as a result of heart failure

muscle phenotype

trabecula carnea hypoplasia
- at E10.5, mutant embryos with a thin ventricular myocardium exhibit poor inner trabeculation
- in contrast, endocardial cushions appear unaffected

abnormal myocardium layer morphology

thin myocardium
- at E10.5, ~80% of mutant embryos display a thinner ventricular myocardium than wild-type embryos

cardiovascular system phenotype

trabecula carnea hypoplasia
- at E10.5, mutant embryos with a thin ventricular myocardium exhibit poor inner trabeculation
- in contrast, endocardial cushions appear unaffected

internal hemorrhage
- ~50% of mutant embryos surviving at E11.5 exhibit signs of abdominal hemorrhage, despite normal development of the vascular endothelium

abnormal myocardium layer morphology

thin myocardium
- at E10.5, ~80% of mutant embryos display a thinner ventricular myocardium than wild-type embryos

cellular phenotype

decreased fibroblast apoptosis
- in contrast, no differences are observed in DR4-, oncogene (E1A and Myc)- or drug (adriamycin)- induced apoptosis relative to wild-type cells
- mutant embryonic fibroblast cells show impaired apoptosis-inducing signaling by Fas, Tnfrsf1a, and Tnfrsf25 (also known as death receptor 3, DR3)

embryo phenotype

decreased embryo size
- at E11.5, ~80% of homozygotes are smaller in size relative to wild-type embryos

embryonic growth retardation
- at E11.5, ~80% of homozygotes appear underdeveloped and growth retarded relative to wild-type embryos, despite normal placental development and absence of excessive apoptosis or reduced cellular proliferation

References

Yeh WC; Pompa JL; McCurrach ME; Shu HB; Elia AJ; Shahinian A ; Ng M ; Wakeham A ; Khoo W ; Mitchell K ; El-Deiry WS ; Lowe SW ; Goeddel DV ; Mak TW. 1998. FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis. Science 279(5358):1954-8PubMed: 9506948 MGI: J:46527

Additional - Fadd^tm1Mak related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Fadd
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664). Homozygotes are not viable.
- Additional Breeding and Husbandry Support
Citation
When using the Fadd Knock-out mouse strain in a publication, please cite the originating article(s) and include JAX stock #029255 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 Fadd<tm1Mak>

Related Products and Services

Frozen Mouse Embryo	B6;129P2-Fadd<tm1Mak>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129P2-Fadd<tm1Mak>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129P2-Fadd<tm1Mak>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6;129P2-Fadd<tm1Mak>/J Frozen Embryo	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

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

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Fadd Knock-out

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Faddtm1Mak

Allele Symbol: Faddtm1Mak

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Faddtm1Mak/Faddtm1Makeither: (involves: 129P2/OlaHsd * C57BL/6J) or (involves: 129P2/OlaHsd * CD-1)

growth/size/body region phenotype

mortality/aging

muscle phenotype

cardiovascular system phenotype

cellular phenotype

embryo phenotype

References

Additional - Faddtm1Mak 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

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Fadd^tm1Mak

Allele Symbol: Fadd^tm1Mak

Genotype: Fadd^tm1Mak/Fadd^tm1Mak
either: (involves: 129P2/OlaHsd * C57BL/6J) or (involves: 129P2/OlaHsd * CD-1)

Additional - Fadd^tm1Mak related