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 MRL.CBAJms-Tnfrsf6lpr-cg/J    (Changed: 26-JAN-05 ) Faslpr-cg    (Changed: 15-DEC-04 ) Type Congenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain MRL/MpJ Donor Strain CBA/KlJms Generation NE12F?+36pN1 Generation Definitions

Appearance
albino
Related Genotype: a/a Tyr^c/Tyr^c

Description
Mice homozygous for the lymphoproliferation complementing gld spontaneous mutation (Fas^lpr-cg) are viable and fertile. Homozygous mutant mice are characterized by massive lymphadenopathy. Fas^lpr-cg complemented both Fas^lpr and the Fasl^gld mutation in that double heterozygotes with either mutation had lymphadenopathy. However, further crosses showed the new mutation to be an allele at Fas^lpr. Like Fas^lpr and Fasl^gld homozygotes, CBA/KlJms-Fas^lpr-cg homozygotes (Stock No. 001876) produce antibodies to some nuclear antigens, such as dsDNA, ssDNA, and poly(ADP-ribose); however, they do not produce anti-erythrocyte antibodies. Although they exhibit lymphoid cell infiltration around blood vessels in lung, liver, and kidney, they lack the immune-complex glomerulonephritis, vasculitis, and interstitial pneumonia characteristic of Fas^lpr homozygotes. Fas^lpr-cg homozygotes on the MRL/MpJ genetic background developed glomerulonephritic lesions similar to those of MRL/MpJ-Fas^lpr mutants, but at a lower frequency, suggesting MRL/MpJ background genes control this aspect of the disease.

MRL/MpJ, and one of its ancestral strains LG/J, display heightened wound healing relative to a panel of other inbred strains. At 4 weeks post-injury, 2mm ear punch wounds healed to 0-0.4mm in MRL/MpJ mice but were still 1.2-1.6mm in C57BL/6 mice. At 15 days post-injury C57BL/6 showed a maximal closure of 30% reduction in ear hole size while MRL showed 85% reduction. The process of healing in MRL/MpJ mice was faster, more complete, showed increased swelling, angiogenesis, fibroblast migration, extracellular matrix deposition, and decreased scarring and fibrosis. Additionally, hair follicles and accompanying sebaceous glands were regenerated to a much greater degree. The other ancestral strains of MRL/MpJ (C3H, C57BL/6, and AKR) do not display this enhanced healing. Bone marrow transplantation showed that the MRL/MpJ healing phenotype did not readily transfer with bone marrow and did remain in the irradiated host tissues. Enhanced healing of cardiac wounds has also been reported in MRL/MpJ mice. In this model a very high mitotic index (10-20%) was found, similar to that seen in non-mammalian tissue regeneration. Using F2 and backcross mapping of MRL/MpJ-Tnfrsf6^lpr x B6 progeny McBrearty et al. identified wound healing QTLs: the heal2 and heal3 loci were identified on MRL/MpJ chromosome 13 in the region of D13Mit115 and D13Mit129 respectively; the heal5 locus was identified on MRL/MpJ chromosome 12 in the region of D12Mit233; the heal1 locus was identified on chromosome 8 of C57BL/6 in the region of D8Mit211; and a highly suggestive locus was found on MRL/MpJ chromosome 7 in the region of D7Mit220. (Clark et al., 1998; Leferovich et al., 2001; Kench et al., 1999; McBrearty et al., 1998.)

Microarray analysis and SELDI ProteinChip analysis have identified multiple genes and proteins that have varied expression in the ear punch wounds of MRL/MpJ-Tnfrsf6^lpr versus C57BL/6. The changes in expression patterns suggest that in MRL/MpJ mice there is less of an inflammatory response and an earlier transition into tissue repair than is seen in C57BL/6. (Li et al., 2000 and 2001.)

Blankenhorn et al. found that MRL/MpJ females heal faster and more completely than males. Some heal QTL are sexually dimorphic with heal 2, 3, 7, 8, 10,and 11 having greater effect in males and heal 4, 5,and 9 having greater effect in females. Castration improves wound healing in MRL/MpJ males to nearly the degree seen in females, but ovariectomy does not improve the degree of healing seen in MRL/MpJ females. (Blankenhorn et al., 2003)

Relative to B10.D2nSnJ mice, MRL/MpJ mice have decreased Neutrophil accumulation in the bronchiolar lavage in response to LPS infusion and tests using bone marrow chimeras revealed that the pulmonary inflammatory response transfers with bone marrow. Transforming growth factor beta 1 autologous induction is reduced in MRL/MpJ splenocytes while macrophages show a reduction in the transforming growth factor beta 1induction of interleukin 1 beta and tumor necrosis factor alpha production but no significant reduction in transforming growth factor beta 1 production. (Kench et al., 1999.)

Development
The Fas^lpr-cg mutation occurred spontaneously in a subline of the inbred strain CBA/KlJms maintained at the Institute of Medical Science in Tokyo.

Control Information

	Control
	000486 MRL/MpJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Fas^lpr-cg allele

001876

CBA/KlJms-Faslpr-cg/J

View Strains carrying   Fas^lpr-cg     (1 strain)

Strains carrying other alleles of Fas

003233	B6.129P2-Fastm1Osa/J
000482	B6.MRL-Faslpr/J
000480	C3.MRL-Faslpr/J
007895	C57BL/6-Fastm1Cgn/J
003234	MRL.129P2(B6)-Fastm1Osa/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^lpr-cg/Fas^lpr-cg

        CBA/KlJms-Fas^lpr-cg/J

• mortality/aging
• premature death
  • earliest deaths at 19 and 29 weeks of age   (MGI Ref ID J:24805)
  • survival rate at 1 year is 61.1% in males and 46.2% in females   (MGI Ref ID J:24805)
• immune system phenotype
• abnormal T cell differentiation
  • anomalous differentiation of T cells, with anomalous expression of surface antigens   (MGI Ref ID J:24805)
• abnormal hypersensitivity reaction   (MGI Ref ID J:81770)
  • lymphocyte infiltration in liver, lungs, spleen, and kidneys   (MGI Ref ID J:24805)
• abnormal lymph organ size   (MGI Ref ID J:24805)
• • enlarged lymph nodes   (MGI Ref ID J:81770)
    • enlargement of the superficial lymph nodes starts at about 2.5 months of age, with cervical preceding inguinal lymph nodes   (MGI Ref ID J:24805)
    • superficial lymph nodes are more than 5 and 15 times heavier than controls at 3 and 5 months of age, respectively   (MGI Ref ID J:24805)
    • mesenteric lymph nodes are normal in size   (MGI Ref ID J:24805)
  • enlarged spleen
    • palpable by 3 months of age   (MGI Ref ID J:24805)
  • • increased spleen weight
      • spleens larger in females than males   (MGI Ref ID J:81770)
      • spleen weights increase up to 6 months of age and remain at a plateau thereafter   (MGI Ref ID J:81770)
• autoimmune response   (MGI Ref ID J:24805)
• • increased autoantibody level   (MGI Ref ID J:81770)
  • • increased anti-nuclear antigen antibody level
      • elevated levels of autoantibodies to nuclear antigens including anti-DNA   (MGI Ref ID J:24805)
• increased immunoglobulin level   (MGI Ref ID J:24805)
• • increased IgG level   (MGI Ref ID J:24805)
    • five times higher than in controls   (MGI Ref ID J:81770)
  • increased IgM level   (MGI Ref ID J:24805)
    • two times higher than in controls   (MGI Ref ID J:81770)
• hematopoietic system phenotype
• abnormal T cell differentiation
  • anomalous differentiation of T cells, with anomalous expression of surface antigens   (MGI Ref ID J:24805)
• enlarged spleen
  • palpable by 3 months of age   (MGI Ref ID J:24805)
• • increased spleen weight
    • spleens larger in females than males   (MGI Ref ID J:81770)
    • spleen weights increase up to 6 months of age and remain at a plateau thereafter   (MGI Ref ID J:81770)
• cellular phenotype
• abnormal T cell differentiation
  • anomalous differentiation of T cells, with anomalous expression of surface antigens   (MGI Ref ID J:24805)

View Research Applications

Research Applications

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

Fas^lpr-cg related

Apoptosis Research
Death Receptors

Cancer Research
Genes Regulating Growth and Proliferation

Immunology, Inflammation and Autoimmunity Research
Autoimmunity
      lupus erythematosus
Inflammation

Mouse/Human Gene Homologs
autoimmune lymphoproliferative syndrome

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Faslpr-cg
Allele Name		lymphoproliferation complementing gld
Allele Type		Spontaneous
Common Name(s)		lprcg;
Strain of Origin		CBA/KlJms
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;
General Note		This mutation, which produces massive lymphadenopathy in homozygotes, occurred spontaneously in a subline of the inbred strain CBA/KlJms maintained at the Institute of Medical Science in Tokyo. Faslpr-cg complemented both Faslpr andthe generalized lymphoproliferative disease Faslgld mutation in that double heterozygotes with either mutation had lymphadenopathy. However, further crosses showed the new mutation to be an allele at Faslpr (J:24805). Like Faslpr and Faslgld mutant homozygotes, CBA-Faslpr-cg/Faslpr-cg mutants produce antibodies to some nuclear antigens, such as dsDNA, ssDNA, and poly(ADP-ribose); however, they do not produce anti-erythrocyte antibodies. Although they exhibit lymphoid cell infiltration around blood vessels in lung, liver, and kidney, they lack the immune-complex glomerulonephritis, vasculitis, and interstitial pneumonia characteristic of Faslpr homozygotes (J:616). Faslpr-cg homozygotes on the MRL genetic background developed glomerulonephritic lesions similar to those of MRL/MpJ-Faslpr mutants, although at a lower frequency, suggesting MRL/MpJ background genes control this aspect of the disease (J:1753). Studies of Faslpr and Faslpr-cg homozygotes in athymic nude (Hfh11nu/Hfh11nu) mice show that the thymus is critical for lymphadenopathy and autoimmunity (J:582).
Molecular Note		A T-to-A transversion point mutation at nucleotide 786 results in replacement by asparagine of a highly conserved isoleucine in the cytoplasmic region of the encoded protein. [MGI Ref ID J:1181]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Clark LD; Clark RK; Heber-Katz E. 1998. A new murine model for mammalian wound repair and regeneration. Clin Immunol Immunopathol 88(1):35-45. [PubMed: 9683548]  [MGI Ref ID J:48937]

Kimura M; Ogata Y; Shimada K; Moriyama T; Matsuzawa A. 1991. New mutant mice of autoimmunity, CBA/KiJms-lprcg/lprcg, that could link the lpr and gld genes [letter] Autoimmunity 9(4):359-61. [PubMed: 1954317]  [MGI Ref ID J:616]

Kimura M; Ogata Y; Shimada K; Wakabayashi T; Onoda H; Katagiri T; Matsuzawa A. 1992. Nephritogenicity of the lprcg gene on the MRL background. Immunology 76(3):498-504. [PubMed: 1526655]  [MGI Ref ID J:1753]

Li X; Mohan S; Gu W; Baylink DJ. 2001. Analysis of gene expression in the wound repair/regeneration process. Mamm Genome 12(1):52-9. [PubMed: 11178744]  [MGI Ref ID J:68684]

Li X; Mohan S; Gu W; Miyakoshi N; Baylink DJ. 2000. Differential protein profile in the ear-punched tissue of regeneration and non-regeneration strains of mice: a novel approach to explore the candidate genes for soft-tissue regeneration Biochim Biophys Acta 1524(2-3):102-9. [PubMed: 11113556]  [MGI Ref ID J:66437]

Matsuzawa A; Moriyama T; Kaneko T; Tanaka M; Kimura M; Ikeda H; Katagiri T. 1990. A new allele of the lpr locus, lprcg, that complements the gld gene in induction of lymphadenopathy in the mouse. J Exp Med 171(2):519-31. [PubMed: 2406366]  [MGI Ref ID J:24805]

Fas^lpr-cg related

Ashany D; Savir A; Bhardwaj N; Elkon KB. 1999. Dendritic cells are resistant to apoptosis through the Fas (CD95/APO-1) pathway. J Immunol 163(10):5303-11. [PubMed: 10553053]  [MGI Ref ID J:118433]

Desbarats J; Newell MK. 2000. Fas engagement accelerates liver regeneration after partial hepatectomy. Nat Med 6(8):920-3. [PubMed: 10932231]  [MGI Ref ID J:118048]

Kimura M; Matsuzawa A. 1994. Autoimmunity in mice bearing lprcg: a novel mutant gene. Int Rev Immunol 11(3):193-210. [PubMed: 7930845]  [MGI Ref ID J:21991]

Kimura M; Mohri H; Shimada K; Wakabayashi T; Kanai Y; Matsuzawa A. 1990. Serological and histological characterization of the new mutant strain of lpr mice, CBA/KlJms-lprcg/lprcg. Clin Exp Immunol 79(1):123-9. [PubMed: 2302830]  [MGI Ref ID J:81770]

Kimura M; Ogata Y; Shimada K; Moriyama T; Matsuzawa A. 1991. New mutant mice of autoimmunity, CBA/KiJms-lprcg/lprcg, that could link the lpr and gld genes [letter] Autoimmunity 9(4):359-61. [PubMed: 1954317]  [MGI Ref ID J:616]

Kimura M; Ogata Y; Shimada K; Wakabayashi T; Onoda H; Katagiri T; Matsuzawa A. 1992. Nephritogenicity of the lprcg gene on the MRL background. Immunology 76(3):498-504. [PubMed: 1526655]  [MGI Ref ID J:1753]

Lopez AD; Avasarala S; Grewal S; Murali AK; London L. 2009. Differential role of the Fas/Fas ligand apoptotic pathway in inflammation and lung fibrosis associated with reovirus 1/L-induced bronchiolitis obliterans organizing pneumonia and acute respiratory distress syndrome. J Immunol 183(12):8244-57. [PubMed: 20007588]  [MGI Ref ID J:157457]

Matsuzawa A; Katagiri T; Ogata Y; Kominami R; Kimura M. 1994. Lymphadenopathy induced by the cooperation between lprcg and gld genes is of lpr but not of gld phenotype. Eur J Immunol 24(7):1714-6. [PubMed: 8026532]  [MGI Ref ID J:19735]

Matsuzawa A; Moriyama T; Kaneko T; Tanaka M; Kimura M; Ikeda H; Katagiri T. 1990. A new allele of the lpr locus, lprcg, that complements the gld gene in induction of lymphadenopathy in the mouse. J Exp Med 171(2):519-31. [PubMed: 2406366]  [MGI Ref ID J:24805]

Matsuzawa A; Moriyama T; Ogata Y; Katagiri T; Kimura M. 1992. A crucial role of the thymus in induction by the lprcg gene of lymphadenopathy with autoimmunity in the mouse. Immunology 75(4):688-92. [PubMed: 1592441]  [MGI Ref ID J:582]

Matsuzawa A; Shimizu M; Takeda Y; Nagase H; Sayama K; Kimura M. 2002. Significant role of Fas ligand-binding but defective Fas receptor (CD95) in lymph node hyperplasia composed of abnormal double-negative T cells. Immunology 106(4):470-5. [PubMed: 12153509]  [MGI Ref ID J:78449]

Nagata S. 1994. Mutations in the Fas antigen gene in lpr mice. Semin Immunol 6(1):3-8. [PubMed: 7513193]  [MGI Ref ID J:19057]

Nambu H; Yuge K; Shikata N; Tsubura A; Matsuzawa A. 1996. Fas-independent apoptosis of photoreceptor cells in C3H mice. Exp Anim 45(4):309-15. [PubMed: 8902493]  [MGI Ref ID J:36218]

Ogata Y; Kimura M; Shimada K; Wakabayashi T; Onoda H; Katagiri T; Matsuzawa A. 1993. Distinctive expression of lprcg in the heterozygous state on different genetic backgrounds. Cell Immunol 148(1):91-102. [PubMed: 8495493]  [MGI Ref ID J:4985]

Ohno T; Kobayashi F; Nishimura M. 2005. Fas has a role in cerebral malaria, but not in proliferation or exclusion of the murine parasite in mice. Immunogenetics 57(3-4):293-6. [PubMed: 15900502]  [MGI Ref ID J:98532]

Rosenblatt N; Hartmann KU; Loor F. 1994. The Yaa mutation induces the development of autoimmunity in mice heterozygous for the gld (generalized lymphadenopathy disease) mutation. Cell Immunol 156(2):519-28. [PubMed: 8025960]  [MGI Ref ID J:19169]

Shimizu M; Sekine K; Matsuzawa A; Iwaguchi T. 1992. Cell electrophoretic characterization of abnormally expanded lymphocytes in autoimmune lprcg, lpr, gld and Yaa mice, and of thymocyte subsets. Electrophoresis 13(3):136-42. [PubMed: 1592043]  [MGI Ref ID J:2361]

Teachey DT; Seif AE; Brown VI; Bruno M; Bunte RM; Chang YJ; Choi JK; Fish JD; Hall J; Reid GS; Ryan T; Sheen C; Zweidler-McKay P; Grupp SA. 2008. Targeting Notch signaling in autoimmune and lymphoproliferative disease. Blood 111(2):705-14. [PubMed: 17925488]  [MGI Ref ID J:130092]

Watanabe T; Sakai Y; Hanai A; Masaki S; Ohno K; Miyawaki S; Matsuzawa A. 1993. A new allele at the lpr gene on mouse chromosome 19 expresses properties different from the original recessive mutation. Mamm Genome 4(6):346-7. [PubMed: 8318739]  [MGI Ref ID J:13031]

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]

Watson ML; Rao JK; Gilkeson GS; Ruiz P; Eicher EM; Pisetsky DS; Matsuzawa A; Rochelle JM; Seldin MF. 1992. Genetic analysis of MRL-lpr mice: relationship of the Fas apoptosis gene to disease manifestations and renal disease-modifying loci. J Exp Med 176(6):1645-56. [PubMed: 1460423]  [MGI Ref ID J:3304]

Yasuda T; Yoshimoto T; Tsubura A; Matsuzawa A. 2001. Clear suppression of Th1 responses but marginal amelioration of autoimmune manifestations by IL-12p40 transgene in MRL-FAS(lprcg)/FAS(lprcg) mice. Cell Immunol 210(2):77-86. [PubMed: 11520074]  [MGI Ref ID J:71348]

Yasuda T; Zhang Y; Nagase H; Kaneko T; Sayama K; Hashimoto H; Matsuzawa A. 2000. Immunological characterization of C3H mice congenic for Fas(lprcg), C3h/HeJ-Fas(lprcg)/Fas(lprcg). Lab Anim 34(1):46-55. [PubMed: 10759366]  [MGI Ref ID J:59981]

Zuliani C; Kleber S; Klussmann S; Wenger T; Kenzelmann M; Schreglmann N; Martinez A; del Rio JA; Soriano E; Vodrazka P; Kuner R; Groene HJ; Herr I; Krammer PH; Martin-Villalba A. 2006. Control of neuronal branching by the death receptor CD95 (Fas/Apo-1). Cell Death Differ 13(1):31-40. [PubMed: 16003386]  [MGI Ref ID J:121029]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	Due to the heightened healing which occurs in mice with the MRL genetic background, ear punch is not expected to be a good method for individual mouse identification in this strain.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• View the complete collection of spontaneous mutants in the Mouse Mutant Resource.

Control Information

	Control
	000486 MRL/MpJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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