Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.129P2-Tnfrsf6tm1Osa/J    (Changed: 26-JAN-05 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129P2 via E14TG2a ES cell line Generation F?+7pN1 Generation Definitions   Donating Investigator Dr. 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
002983	MRL.CBAJms-Faslpr-cg/J
002455	MRL.Cg-B2mtm1Unc Faslpr
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)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Autoimmune Lymphoproliferative Syndrome; ALPS

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      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

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

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

Internal/Organ Research
Spleen Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Fastm1Osa
Allele Name		targeted mutation 1, Osaka University Medical School
Allele Type		Targeted (Reporter)
Common Name(s)		Fas-; Tnfrsf6tm1Osa;
Mutation Made By		Dr. 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; TNF receptor superfamily member 6; TNFR6; TNFRSF6; Tnfrsf6; expressed sequence AI196731; lpr; lymphoproliferation;
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, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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]

Kovacic N; Grcevic D; Katavic V; Lukic IK; Grubisic V; Mihovilovic K; Cvija H; Croucher PI; Marusic A. 2010. Fas receptor is required for estrogen deficiency-induced bone loss in mice. Lab Invest 90(3):402-13. [PubMed: 20084056]  [MGI Ref ID J:157592]

Kovacic N; Lukic IK; Grcevic D; Katavic V; Croucher P; Marusic A. 2007. The Fas/Fas ligand system inhibits differentiation of murine osteoblasts but has a limited role in osteoblast and osteoclast apoptosis. J Immunol 178(6):3379-89. [PubMed: 17339432]  [MGI Ref ID J:144295]

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]

Larena M; Regner M; Lee E; Lobigs M. 2011. Pivotal role of antibody and subsidiary contribution of CD8+ T cells to recovery from infection in a murine model of Japanese encephalitis. J Virol :. [PubMed: 21450826]  [MGI Ref ID J:171204]

Lee SK; Silva DG; Martin JL; Pratama A; Hu X; Chang PP; Walters G; Vinuesa CG. 2012. Interferon-gamma excess leads to pathogenic accumulation of follicular helper T cells and germinal centers. Immunity 37(5):880-92. [PubMed: 23159227]  [MGI Ref ID J:190440]

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]

Yang PL; Althage A; Chung J; Maier H; Wieland S; Isogawa M; Chisari FV. 2010. Immune effectors required for hepatitis B virus clearance. Proc Natl Acad Sci U S A 107(2):798-802. [PubMed: 20080755]  [MGI Ref ID J:156523]

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]

de Claro RA; Zhu X; Tang J; Morgan-Stevenson V; Schwartz BR; Iwata A; Liles WC; Raines EW; Harlan JM. 2011. Hematopoietic Fas Deficiency Does Not Affect Experimental Atherosclerotic Lesion Formation despite Inducing a Proatherogenic State. Am J Pathol 178(6):2931-7. [PubMed: 21550016]  [MGI Ref ID J:173162]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
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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