Strain Name: |
C3.MRL-Faslpr/J |
|---|---|
Stock Number: |
000480 |
Availability: | Repository- Live |
General Terms and Conditions |
| Former Name |
C3.MRL-Tnfrsf6lpr/J (Changed: 26-JAN-05
) |
| Genes & Alleles | Fas; Faslpr; Pde6b; Pde6brd1; |
Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Spontaneous Mutation Mating System Homozygote x Homozygote (Female x Male) Species laboratory mouse Background Strain C3H/HeJ Donor Strain MRL/MpJ-Faslpr H2 Haplotype k Generation N10F84 (22-JAN-08) Appearance
agouti
Related Genotype: A/AImportant Note
This strain is homozygous for the retinal degeneration allele Pde6brd1.Strain Description
Mice homozygous for the lymphoproliferation spontaneous mutation (Faslpr) show systemic autoimmunity, massive lymphadenopathy associated with proliferation of aberrant T cells, arthritis, and immune complex glomerulonephrosis. Onset and severity of symptoms associated with the Faslpr allele is strain-dependent. For example, lymphoproliferation varies greatly with congenic strain C57BL/6J-Faslpr/Faslpr at a 24 fold increase over control lymph node weight, MRL/Mp-Faslpr/Faslpr at 75 fold and congenic strain C3H/HeJ-Faslpr/Faslpr highest at 116 fold increase over control lymph node weight (Morse et al 1985). Variance in renal pathology ranks from extensive in MRL/Mp-Faslpr/Faslpr at 4 to 7 months to negligible at 14 to 16 months in mice with C57BL/6J and C3H/HeJ backgrounds and homozygous for Faslpr (Kelley and Roths 1985). Spontaneous production of anti-dsDNA autoantibodies is likewise affected with percentage binding of radiolabeled dsDNA in Faslpr/Faslpr mice varying from 5 percent on C57BL/6J to 26 percent on C3H/HeJ to as high as 49 percent on MRL/Mp (Izui et al 1984). Female MRL/Mp-Faslpr mice die at an average age of 17 weeks of age and males at 22 weeks. This compares to between 42 and 52 weeks in females on the C57BL/6J or C3H/HeJ background (Roths 1987). This mouse is a model for systemic lupus erythematosus-like autoimmune syndromes.In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
Related Disease (OMIM) Terms |
Mammalian Phenotype Terms assigned by genotype |
| Allele Symbol | Faslpr | ||
|---|---|---|---|
| Allele Name | lymphoproliferation | ||
| Common Name(s) | Fas-; Tnfrf6lpr; Tnfrsf6lpr; Tnfrsf6lpr; lpr; | ||
| Strain of Origin | MRL/Mp | ||
| 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; | ||
| General Note |
Faslpr, lymphoproliferation, recessive. This mutation was found during inbreeding of a strain MRL/Mp derived from crosses among strains LG, AKR, C3H, and C57BL/6. MRL/Mp mice homozygous for the Faslpr mutation develop an autoimmune syndrome with massive lymphoproliferation and immune complex glomerulonephrosis beginning by 8 weeks of age. Females die at an average age of 17 weeks and males at 22 weeks (J:13747, J:13757). Hypergammaglobulinemia develops with twofold increases in IgA,IgM, and IgG2b, and 10-fold increases in IgG1 and IgG2a (J:28885). The excess lymphocyte population consists largely of antigenically abnormal T-cells (J:7094)(J:6902). There is enhanced T-helper cell activity (J:6257) and an early-onset generalized polyclonal B-cell activation, which does not, however, occur until after appearance of the abnormal T-cells in the spleen and lymph nodes (J:7488). The abnormal T-cells are descended from abnormal bone-marrow stem cells that require processing in the thymus to acquire their abnormal surface markers (J:7617)(J:6399)(J:6542). There is a progressive defect in ability of lymphocytes to produce and respond to interleukin 2 (J:6638) and an increase in expression of Il3 (J:7504). Transfer of wild-type spleen or bonemarrow cells into Faslpr/Faslpr mice delays the onset of autoimmunity and increases longevity to almost normal. Transfer of Faslpr/Faslpr cells to wild-type mice causes severe graft vs. host disease, wasting, and early death. A proposed explanation of these results is that Faslpr/Faslpr cells intrinsically lack an antigen that is present on wild-type cells and is recognized as foreign by the transplanted mutant lymphocytes (J:7907). The Fas antigen presumably is the antigen involved in this process. It is further suggested that in the absence of the Fas antigen, lymphocytes fail to undergo apoptosis (J:3304) leading to lymphoproliferation.Disease symptoms are ameliorated in Faslpr/Faslpr mice bearing the X-linked immune deficiency gene Btk, which causes absence of a class of mature B-cells (J:7541)(J:7247). Disease symptoms are also ameliorated by a restricted-calorie diet (J:7603) or by a fish oil diet that reducescyclooxygenase metabolites (J:12027).The Faslpr gene has been introduced into a number of different inbred strains, which can cause varying degrees of lymphoproliferation, autoimmune antibody production, earliness of death, and incidence of severe lupus-like disease (J:7488)(J:7454)(J:7745). For example, the mutation on inbred strains AKR/J, C3H/HeJ, and C57BL/6J, reduces the life span to 42-52 weeks, but on SJL/J or MRL/Mp the reduction is even greater at 17-22 weeks.The mutation Faslgld (generalized lymphoproliferative disease) produces an abnormal T-cell population indistinguishable from that produced by Faslpr (J:8267).The Faslpr syndrome resembles human systemic lupus erythematosus (SLE) (OMIM 152700), an autoimmune disease (J:27634). The resemblance has led to extensive use of Faslpr mice in attempts to determine the etiology of SLE and to evaluate therapies. However, the human APT1 gene (OMIM 134637) encodes the FAS antigen; Tnfrsf6 is not the homolog of the human (SLE) gene.Human female cases of SLE greatly outnumber cases in males, and in mouse models, female mice die earlier than males. Ovariectomy can rescue females, and estrogen treatment can accelerate death in males. Blocking estrogen production can reduce mouse autoimmune expression (J:17560), as can androgen treatment (J:18512).Glomerulonephritis is a feature of both human and mouse lupus. The glomerulonephritis seems to be caused by elevated autoantibody production in the lupus mouse (J:15513). The lupus mouse develops cognitive and neurologic deficits which may be related to mononuclear cell infiltration of the central nervous system (J:14151). Autoimmune thyroiditis is another manifestation of both human and mouse lupus (J:28171).Sjogren syndrome (OMIM 270150), a human autoimmune inflammatory disease, affects the lacrimal and salivary glands. It can occur in conjunction with rheumatoid arthritis or SLE, but also can occur by itself. It is essentially restricted to women. C3H-Faslpr mice showed a lacrimal gland inflammation correlated with the onset of systemic autoimmune disease that closely resembles Sjogren syndrome (J:1028). The submandibular gland is also involved in MRL/MpJ-Faslpr mice. Treatment with androgen or with cyclophosphamide has been shown to reduce autoimmune expression in these Sjogren syndrome models (J:18512). Cells from the inflamed submandibular salivary gland tissue of MRL/MpJ-Faslpr mice, transferred peritoneally into Prkdc mice, caused Sjogren lesions in the host animals. These could be prevented by treating the inoculates with antibodies against CD4 and T-cell receptor Vbeta8 (J:21965). T-cell receptor Vbetaa8 elements are used preferentially in the salivary gland of MRL/MpJ-Faslpr animals (J:28856). It is unknown if mice homozygous for Fas | ||
| Molecular Note | Southern blotting experiments indicated that the mutation is a genomic rearrangement within the gene, probably within intron 2. [J:1181] [J:14206] [J:14503] [J:15429] [J:4166] [J:4342] [J:72675] [J:92470] | ||
| Allele Symbol | Pde6brd1 | ||
| Allele Name | retinal degeneration 1 | ||
| Common Name(s) | rd; rd-1; rd1; rodless retina; | ||
| Allele | Control | |
|---|---|---|
| Faslpr | 000659 C3H/HeJ | |
| Considerations for Choosing Controls | ||
Faslpr
| Diet Information | LabDiet® 5K52/5K67 |
|---|
Strains carrying Faslpr allele
000482 B6.MRL-Faslpr/J 002455 MRL-Faslpr.129P2(B6)-B2mtm1Unc 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 Faslpr (7 strains)
Strains carrying Pde6brd1 allele
View Strains carrying Pde6brd1 (74 strains)
Strains carrying other alleles of Fas
003233 B6.129P2-Fastm1Osa/J 007895 C57BL/6-Fastm1Cgn/J 001876 CBA/KlJms-Faslpr-cg/J 003234 MRL.129P2(B6)-Fastm1Osa/J 002983 MRL.CBAJms-Faslpr-cg/J View Strains carrying other alleles of Fas (5 strains)
Strains carrying other alleles of Pde6b
004297 B6.CXB1-Pde6brd10/J 002802 C3.BLiA Pde6b+-Krd/J 001979 C3A.BLiA-Pde6b+.O20-Prph2Rd2/J 001912 C3A.BLiA-Pde6b+/J 003648 C3Sn.BLiA-Pde6b+/Dn 004766 C57BL/6J-Pde6brd1-2J/J 004828 FVB.129P2-Pde6b+ Tyrc-ch/AntJ 004808 STOCK Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J View Strains carrying other alleles of Pde6b (8 strains)
Congenic Nomenclature
Genetic Quality Control Annual Report
Room Number FGB29
Faslpr related
Pde6brd1 relatedApoptosis Research
Death Receptors
Cancer Research
Genes Regulating Growth and Proliferation
Immunology and Inflammation Research
Autoimmunity (lupus erythematosus: rheumatoid arthritis)
Inflammation (rheumatoid arthritis)
Mouse/Human Gene Homologs
autoimmune lymphoproliferative syndrome
retinitis pigmentosa, autosomal recessive
Sensorineural Research
Retinal Degeneration
Selected Reference(s)
Additional ReferencesAndrews BS; Eisenberg RA; Theofilopoulos AN; Izui S; Wilson CB; McConahey PJ; Murphy ED; Roths JB; Dixon FJ. 1978. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med 148(5):1198-215. [PubMed: 309911] [J:27634]
Drappa J; Brot N; Elkon KB. 1993. The Fas protein is expressed at high levels on CD4+CD8+ thymocytes and activated mature lymphocytes in normal mice but not in the lupus-prone strain, MRL lpr/lpr. Proc Natl Acad Sci U S A 90(21):10340-4. [PubMed: 7694292] [J:15429]
Hewicker M; Kromschroder E; Trautwein G. 1990. Detection of circulating immune complexes in MRL mice with different forms of glomerulonephritis. Z Versuchstierkd 33(4):149-56. [PubMed: 2238887] [J:109933]
Johnson BC; Morton JI; Trune DR. 1992. Lacrimal and salivary gland inflammation in the C3H/Ipr autoimmune strain mouse: a potential mode for Sjogren's syndrome. Otolaryngol Head Neck Surg 106(4):394-9. [PubMed: 1565490] [J:1028]
Kawase E; Suemori H; Takahashi N; Okazaki K; Hashimoto K; Nakatsuji N. 1994. Strain difference in establishment of mouse embryonic stem (ES) cell lines. Int J Dev Biol 38(2):385-90. [PubMed: 7981049] [J:19823]
Medana I; Li Z; Flugel A; Tschopp J; Wekerle H; Neumann H. 2001. Fas ligand (CD95L) protects neurons against perforin-mediated T lymphocyte cytotoxicity. J Immunol 167(2):674-81. [PubMed: 11441070] [J:109872]
Morse HC 3rd; Davidson WF; Yetter RA; Murphy ED; Roths JB; Coffman RL. 1982. Abnormalities induced by the mutant gene Ipr: expansion of a unique lymphocyte subset. J Immunol 129(6):2612-5. [PubMed: 6815273] [J:6902]
Morse HC 3rd; Roths JB; Davidson WF; Langdon WY; Fredrickson TN; Hartley JW. 1985. Abnormalities induced by the mutant gene, lpr. Patterns of disease and expression of murine leukemia viruses in SJL/J mice homozygous and heterozygous for lpr. J Exp Med 161(3):602-16. [PubMed: 2982991] [J:7745]
Sato EH; Sullivan DA. 1994. Comparative influence of steroid hormones and immunosuppressive agents on autoimmune expression in lacrimal glands of a female mouse model of Sjogren's syndrome. Invest Ophthalmol Vis Sci 35(5):2632-42. [PubMed: 8163351] [J:18512]
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] [J:1181]
Yogi Y; Nakamura K; Suzuki A. 1989. The experimental inoculation with Mycobacterium leprae in autoimmune mice: results of MRL/lpr mice inoculated into the right hind foot (continued). Nippon Rai Gakkai Zasshi 58(4):235-40. [PubMed: 2489281] [J:27853]
| Strain Name: | C3.MRL-Faslpr/J |
| Stock Number: | 000480 |
IMPORTANT NOTE: Prices are based on shipping destination. To view prices, select your shipping destination.
| 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 Mouse Mutant Resource collection. Genomic DNA is available for this strain from the Mouse DNA Resource. |
| Licensing | See General Terms and Conditions below |
| Control Information | View Control Information in Strain Details. |
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