Description

Strain Information

Type Coisogenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation F?+N1F1 (07-JUL-08)   Donating Investigator Klaus Rajewsky,   Immune Disease Institute (formerly CBRI)

Description
Mice homozygous for this "Fas^fl" conditional allele are viable and fertile, with loxP sites flanking exon 9 of the targeted gene. When bred to mice that express Cre recombinase, exon 9 (which encodes the death domain) is deleted in the cre-expressing tissues in the resulting offspring.

These Fas^fl mice may be useful in generating conditional mutations for studying many aspects of immune function. For example, when Fas^fl mice are crossed to a strain expressing Cre recombinase in B lineage cells (see Stock No. 004126 or 006785 ), this mutant mouse strain may be useful in studies of lymphoproliferative disorder. Similarly, when Fas^fl mice are crossed to an interferon inducible strain with widespread Cre recombinase expression (see Stock No. 003556, 005673, or 002527), this mutant mouse strain may be useful in studies of lymphoproliferative disease. Further, deletion of Fas in T cells (by crossing Fas^fl mice to a CD4-cre transgenic strain) produces mice that develop progressive lymphopenia and inflammatory pulmonary fibrosis which resembles idiopathic pulmonary fibrosis in humans.

Development
A targeting vector was designed to place a loxP-flanked neo cassette downstream, and a third loxP site upstream of exon 9 of the targeted gene. The construct was electroporated into C57BL/6-derived Bruce-4 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a cre-expressing plasmid to remove the neo selection cassette. Chimeric mice were bred to C57BL/6 mice. The resulting "Fas^fl" mice (with a single loxP site just upstream, and a single loxP site just downstream of exon 9) were maintained as homozygotes on the C57BL/6 genetic background prior to arrival at The Jackson Laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Fas

003233	B6.129P2-Fastm1Osa/J
000482	B6.MRL-Faslpr/J
000480	C3.MRL-Faslpr/J
001876	CBA/KlJms-Faslpr-cg/J
002455	MRL-Faslpr.129P2(B6)-B2mtm1Unc
003234	MRL.129P2(B6)-Fastm1Osa/J
002983	MRL.CBAJms-Faslpr-cg/J
003896	MRL/MpJ Faslpr-Foxq1sa-J/J
006825	MRL/MpJ-Faslpr/2J
000485	MRL/MpJ-Faslpr/J
004519	NOD.MRL(C3)-Faslpr/DoiJ
004922	NOD.MRL-Faslpr/Dvs

View Strains carrying other alleles of Fas     (12 strains)

Additional Web Information

Cre-lox Systems

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Fas^tm1Cgn/Fas^tm1Cgn

        C57BL/6-Fas^tm1Cgn

• immune system phenotype
• *normal* immune system phenotype (MGI Ref ID J:114948)
  • normal lymphocyte development and subset distribution

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

Cd19^tm1(cre)Cgn/Cd19⁺ Fas^tm1Cgn/Fas^tm1Cgn

        B6.Cg-Cd19^tm1(cre)Cgn Fas^tm1Cgn   (conditional)

• immune system phenotype
• increased anti-single stranded DNA antibody level (MGI Ref ID J:114948)
  • 3- to 8-fold increase in IgM and IgG antibodies for single stranded DNA; however, this is 2- to 3-fold lower than in mice homozygous for Fas^tm1.1Cgn and mice do not display the increase in double negative T cells or lymphoproliferative disease seen in Fas^lpr homozygotes

Fas^tm1Cgn/Fas^tm1Cgn Tg(Mx1-cre)1Cgn/0

        B6.Cg-Fas^tm1Cgn Tg(Mx1-cre)1Cgn   (conditional)

• immune system phenotype
• abnormal immune system morphology (MGI Ref ID J:114948)
  • after Poly(I) Poly(C) induction of cre expression mice develop the lymphoproliferative disease seen in Fas^tm1.1Cgn homozygtes
• enlarged lymph nodes (MGI Ref ID J:114948)
• enlarged spleen (MGI Ref ID J:114948)
• hematopoietic system phenotype
• enlarged spleen (MGI Ref ID J:114948)

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

Research Tools
Cell Biology Research
Cre-lox System (loxP-flanked Sequences)
Hematological Research
Immunology and Inflammation Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Fastm1Cgn
Allele Name		targeted mutation 1, University of Cologne
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		fasfl;
Mutation Made By		Klaus Rajewsky,   Immune Disease Institute (formerly CBRI)
Strain of Origin		C57BL/6
ES Cell Line Name		Bruce 4
ES Cell Line Strain		C57BL/6
Gene Symbol and Name		Fas, Fas (TNF receptor superfamily member 6)
Chromosome		19
Gene Common Name(s)		AI196731; ALPS1A; APO-1; APT1; CD95; FAS1; FASTM; Fas antigen; TNFR6; TNFRSF6; Tnfrsf6; expressed sequence AI196731; lpr; lymphoproliferation; tumor necrosis factor receptor superfamily, member 6;
Molecular Note		Exon 9, the death domain encoding exon, was flanked by loxP sites via homologous recombination. [MGI Ref ID J:114948]

Genotyping

Genotyping Information

Genotyping Protocols

Fas^tm1Cgn, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Hao Z; Hampel B; Yagita H; Rajewsky K. 2004. T cell-specific ablation of Fas leads to Fas ligand-mediated lymphocyte depletion and inflammatory pulmonary fibrosis. J Exp Med 199(10):1355-65. [PubMed: 15148335]  [MGI Ref ID J:114948]

Additional References

Fas^tm1Cgn related

Hovelmeyer N; Hao Z; Kranidioti K; Kassiotis G; Buch T; Frommer F; von Hoch L; Kramer D; Minichiello L; Kollias G; Lassmann H; Waisman A. 2005. Apoptosis of oligodendrocytes via Fas and TNF-R1 is a key event in the induction of experimental autoimmune encephalomyelitis. J Immunol 175(9):5875-84. [PubMed: 16237080]  [MGI Ref ID J:114741]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
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

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional Licensing and Use Restrictions view the link(s) below:
- Notice Regarding cre/Esr1 (Tamoxifen Inducible Cre) Strains.
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.