Description

Strain Information

Former Names B6.129P2-Tnfrsf6tm1Osa/J    (Changed: 26-JAN-05 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129P2 via E14TG2a ES cell line Generation F?+7pN1   Donating Investigator Shigekazu Nagata,   Osaka University Medical School, B-3

Description
Mice homozygous for the Tnfrsf6^tm1Osa targeted mutation mice show hyperplasia in the liver in an age-dependent manner. Hepatocytes contain enlarged nuclei characteristic of senescent cells. Lymphadenopathy and splenomegaly in FAS deficient mice are evident at 8 weeks of age. The lymphnodes and spleen become progressively larger, becoming about 10 and 40 times larger than those of wildtype or heterozygotes at 16 weeks of age, respectively.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Fas^tm1Osa allele

003234

MRL.129P2(B6)-Fastm1Osa/J

View Strains carrying   Fas^tm1Osa     (1 strain)

Strains carrying other alleles of Fas

000482	B6.MRL-Faslpr/J
000480	C3.MRL-Faslpr/J
007895	C57BL/6-Fastm1Cgn/J
001876	CBA/KlJms-Faslpr-cg/J
002455	MRL-Faslpr.129P2(B6)-B2mtm1Unc
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     (11 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Autoimmune Lymphoproliferative Syndrome; ALPS - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Fas^tm1Osa/Fas^tm1Osa

        involves: 129P2/OlaHsd * C57BL/6

• life span-post-weaning/aging
• premature death (MGI Ref ID J:64296)
  • 50% dead at about 5 months of age
• liver/biliary system phenotype
• abnormal hepatocyte morphology (MGI Ref ID J:64296)
  • hepatocyte nuclear areas are variable and larger
• liver hyperplasia (MGI Ref ID J:64296)
  • significantly heavier at 12 weeks of age and becomes 50-60% heavier by 16 weeks of age
  • number of hepatocytes per each liver lobe is increased
• immune system phenotype
• abnormal T cell clonal deletion (MGI Ref ID J:32125)
  • peripheral clonal deletion of mature T cells against a bacterial superantigen is impaired
• abnormal lymph organ size (MGI Ref ID J:64296)
• enlarged lymph nodes (MGI Ref ID J:32125)
  • lymph nodes become progressively larger
• enlarged spleen (MGI Ref ID J:32125)
  • spleen becomes progressively larger
• lymphoid hyperplasia (MGI Ref ID J:64296)
• hypersensitivity (MGI Ref ID J:32125)
  • occasional infiltration of lymphocytes into tissues such as the lungs and liver
• increased IgG level (MGI Ref ID J:32125)
  • 10-100x higher serum levels of IgG1, IgG2a, IgG2b, and IgG3 at 16 weeks of age
• increased IgG1 level (MGI Ref ID J:32125)
• increased IgG2a level (MGI Ref ID J:32125)
• increased IgG2b level (MGI Ref ID J:32125)
• increased IgG3 level (MGI Ref ID J:32125)
• increased autoantibody level (MGI Ref ID J:32125)
  • 50-500x higher levels of dsDNA and ssDNA autoantibodies at 16 weeks of age
• increased anti-double stranded DNA antibody level (MGI Ref ID J:32125)
• increased anti-single stranded DNA antibody level (MGI Ref ID J:32125)
• increased leukocyte cell number (MGI Ref ID J:32125)
  • 20x higher than in controls, attributable to increased lymphocyte numbers
• increased lymphocyte cell number (MGI Ref ID J:32125)
  • lymphocytosis; progressively accumulate abnromal T cells Thy1⁺ B220⁺ CD4^- CD8 ^-
• increased B cell number (MGI Ref ID J:32125)
  • increase in the number of normal B cells
• increased susceptibility to parasitic infection (MGI Ref ID J:81397)
  • decreased survival after infection with Trypanosoma cruzi even though were able to clear parasites from blood and affected organs
• hematopoietic system phenotype
• abnormal T cell clonal deletion (MGI Ref ID J:32125)
  • peripheral clonal deletion of mature T cells against a bacterial superantigen is impaired
• enlarged spleen (MGI Ref ID J:32125)
  • spleen becomes progressively larger
• increased leukocyte cell number (MGI Ref ID J:32125)
  • 20x higher than in controls, attributable to increased lymphocyte numbers
• increased lymphocyte cell number (MGI Ref ID J:32125)
  • lymphocytosis; progressively accumulate abnromal T cells Thy1⁺ B220⁺ CD4^- CD8 ^-
• increased B cell number (MGI Ref ID J:32125)
  • increase in the number of normal B cells

View Research Applications

Research Applications

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

Fas^tm1Osa related

Apoptosis Research
Death Receptors

Cancer Research
Genes Regulating Growth and Proliferation

Hematological Research
Immunological Defects

Immunology and Inflammation Research
Autoimmunity
CD Antigens, Antigen Receptors, and Histocompatibility Markers

Internal/Organ Research
Spleen Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Fastm1Osa
Allele Name		targeted mutation 1, Osaka University Medical School
Allele Type		Targeted (Reporter)
Common Name(s)		Fas-; Tnfrsf6tm1Osa;
Mutation Made By		Shigekazu Nagata,   Osaka University Medical School, B-3
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14.1
ES Cell Line Strain		129P2/OlaHsd
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		A BetaGal-neo cassette was used to delete a portion of exon 9, which codes for the cytoplasmic domain essential for Fas-mediated apoptosis. Northern blot analysis revealed the expression of a truncated mRNA, representing transcripts from exons 1 though 8 in the thymus, liver, and heart. Immunoprecipitation analysis showed an absence of the wild-type protein as well as a faint presence of what the authors speculated to be a non-functional Tnfrsf6-BetaGal fusion protein. [MGI Ref ID J:64296]

Genotyping

Genotyping Information

Genotyping Protocols

Fas^tm1Osa, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Adachi M; Suematsu S; Kondo T; Ogasawara J; Tanaka T; Yoshida N; Nagata S. 1995. Targeted mutation in the Fas gene causes hyperplasia in peripheral lymphoid organs and liver. Nat Genet 11(3):294-300. [PubMed: 7581453]  [MGI Ref ID J:64296]

Additional References

Adachi M; SuematsuS; Suda T; Watanabe D; FukuyamaH; Ogasawara J; Tanaka T; Yoshida N; Nagata S. 1996. Enhanced and accelerated lymphoproliferation in Fas-null mice. Proc Natl Acad Sci U S A 93(5):2131-6. [PubMed: 8700897]  [MGI Ref ID J:32125]

Watanabe-Fukunaga R; Brannan CI; Copeland NG; Jenkins NA; Nagata S. 1992. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356(6367):314-7. [PubMed: 1372394]  [MGI Ref ID J:1181]

Fas^tm1Osa related

Adachi M; SuematsuS; Suda T; Watanabe D; FukuyamaH; Ogasawara J; Tanaka T; Yoshida N; Nagata S. 1996. Enhanced and accelerated lymphoproliferation in Fas-null mice. Proc Natl Acad Sci U S A 93(5):2131-6. [PubMed: 8700897]  [MGI Ref ID J:32125]

Alsharifi M; Lobigs M; Simon MM; Kersten A; Muller K; Koskinen A; Lee E; Mullbacher A. 2006. NK cell-mediated immunopathology during an acute viral infection of the CNS. Eur J Immunol 36(4):887-96. [PubMed: 16541469]  [MGI Ref ID J:114787]

Balkow S; Kersten A; Tran TT; Stehle T; Grosse P; Museteanu C; Utermohlen O; Pircher H; von Weizsacker F; Wallich R; Mullbacher A; Simon MM. 2001. Concerted action of the FasL/Fas and perforin/granzyme A and B pathways is mandatory for the development of early viral hepatitis but not for recovery from viral infection. J Virol 75(18):8781-91. [PubMed: 11507223]  [MGI Ref ID J:71217]

Hayley S; Crocker SJ; Smith PD; Shree T; Jackson-Lewis V; Przedborski S; Mount M; Slack R; Anisman H; Park DS. 2004. Regulation of dopaminergic loss by Fas in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. J Neurosci 24(8):2045-53. [PubMed: 14985447]  [MGI Ref ID J:97007]

Landau AM; Luk KC; Jones ML; Siegrist-Johnstone R; Young YK; Kouassi E; Rymar VV; Dagher A; Sadikot AF; Desbarats J. 2005. Defective Fas expression exacerbates neurotoxicity in a model of Parkinson's disease. J Exp Med 202(5):575-81. [PubMed: 16129703]  [MGI Ref ID J:100698]

Martin SF; Dudda JC; Delattre V; Bachtanian E; Leicht C; Burger B; Weltzien HU; Simon JC. 2004. Fas-mediated inhibition of CD4+ T cell priming results in dominance of type 1 CD8+ T cells in the immune response to the contact sensitizer trinitrophenyl. J Immunol 173(5):3178-85. [PubMed: 15322178]  [MGI Ref ID J:92718]

Meissner NN; Lund FE; Han S; Harmsen A. 2005. CD8 T cell-mediated lung damage in response to the extracellular pathogen pneumocystis is dependent on MHC class I expression by radiation-resistant lung cells. J Immunol 175(12):8271-9. [PubMed: 16339567]  [MGI Ref ID J:122256]

Muller U; Sobek V; Balkow S; Holscher C; Mullbacher A; Museteanu C; Mossmann H; Simon MM. 2003. Concerted action of perforin and granzymes is critical for the elimination of Trypanosoma cruzi from mouse tissues, but prevention of early host death is in addition dependent onthe FasL/Fas pathway. Eur J Immunol 33(1):70-8. [PubMed: 12594834]  [MGI Ref ID J:81397]

Semont A; Nowak EB; Silva Lages C; Mathieu C; Mouthon MA; May E; Allemand I; Millet P; Boussin FD. 2004. Involvement of p53 and Fas/CD95 in murine neural progenitor cell response to ionizing irradiation. Oncogene 23(52):8497-508. [PubMed: 15361846]  [MGI Ref ID J:93854]

Shetty G; Shao SH; Weng CC. 2008. p53-dependent apoptosis in the inhibition of spermatogonial differentiation in juvenile spermatogonial depletion (Utp14bjsd) mice. Endocrinology 149(6):2773-81. [PubMed: 18356279]  [MGI Ref ID J:136072]

Stranges PB; Watson J; Cooper CJ; Choisy-Rossi CM; Stonebraker AC; Beighton RA; Hartig H; Sundberg JP; Servick S; Kaufmann G; Fink PJ; Chervonsky AV. 2007. Elimination of antigen-presenting cells and autoreactive T cells by Fas contributes to prevention of autoimmunity. Immunity 26(5):629-41. [PubMed: 17509906]  [MGI Ref ID J:123556]

Ugolini G; Raoul C; Ferri A; Haenggeli C; Yamamoto Y; Salaun D; Henderson CE; Kato AC; Pettmann B; Hueber AO. 2003. Fas/tumor necrosis factor receptor death signaling is required for axotomy-induced death of motoneurons in vivo. J Neurosci 23(24):8526-31. [PubMed: 13679421]  [MGI Ref ID J:85525]

Watanabe N; Ikuta K; Nisitani S; Chiba T; Honjo T. 2002. Activation and differentiation of autoreactive B-1 cells by interleukin 10 induce autoimmune hemolytic anemia in Fas-deficient antierythrocyte immunoglobulin transgenic mice. J Exp Med 196(1):141-6. [PubMed: 12093879]  [MGI Ref ID J:77493]

Zelinskyy G; Balkow S; Schimmer S; Schepers K; Simon MM; Dittmer U. 2004. Independent roles of perforin, granzymes, and Fas in the control of Friend retrovirus infection. Virology 330(2):365-74. [PubMed: 15567431]  [MGI Ref ID J:95485]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

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.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

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

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.

No Liability

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.