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General Terms and Conditions

Former Name	MRL.CBAJms-Tnfrsf6lpr-cg/J    (Changed: 26-JAN-05 )
	Faslpr-cg    (Changed: 15-DEC-04 )
Genes & Alleles	Fas;   Faslpr-cg;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Spontaneous Mutation Species laboratory mouse Background Strain MRL/MpJ Donor Strain CBA/KlJms Generation NE12F?+36pN1

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

Strain 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.)

Strain 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.

Related Disease (OMIM) Terms Autoimmune Lymphoproliferative Syndrome; ALPS

Mammalian Phenotype Terms assigned by genotype The following phenotype information may relate to a genetic background differing from this JAX® Mice strain. Faslpr-cg/Faslpr-cg         CBA/KlJms-Faslpr-cg/J life span-post-weaning/aging premature death (MGI Ref ID J:24805) earliest deaths at 19 and 29 weeks of age survival rate at 1 year is 61.1% in males and 46.2% in females immune system phenotype abnormal T cell differentiation (MGI Ref ID J:24805) anomalous differentiation of T cells, with anomalous expression of surface antigens 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 superficial lymph nodes are more than 5 and 15 times heavier than controls at 3 and 5 months of age, respectively mesenteric lymph nodes are normal in size enlarged spleen (MGI Ref ID J:24805) palpable by 3 months of age increased spleen weight (MGI Ref ID J:81770) spleens larger in females than males spleen weights increase up to 6 months of age and remain at a plateau thereafter autoimmune response (MGI Ref ID J:24805) increased autoantibody level (MGI Ref ID J:81770) increased anti-nuclear antigen antibody level (MGI Ref ID J:24805) elevated levels of autoantibodies to nuclear antigens including anti-DNA hypersensitivity (MGI Ref ID J:81770) lymphocyte infiltration in liver, lungs, spleen, and kidneys increased immunoglobulin level (MGI Ref ID J:24805) increased IgG level (MGI Ref ID J:24805) five times higher than in controls increased IgM level (MGI Ref ID J:24805) two times higher than in controls hematopoietic system phenotype abnormal T cell differentiation (MGI Ref ID J:24805) anomalous differentiation of T cells, with anomalous expression of surface antigens enlarged spleen (MGI Ref ID J:24805) palpable by 3 months of age increased spleen weight (MGI Ref ID J:81770) spleens larger in females than males spleen weights increase up to 6 months of age and remain at a plateau thereafter

Gene & Allele Details

Allele Symbol		Faslpr-cg
Allele Name		lymphoproliferation complementing gld
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; Fas antigen; TNFR6; TNFRSF6; Tnfrsf6; expressed sequence AI196731; lpr; lymphoproliferation; tumor necrosis factor receptor superfamily, member 6;
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]

Control Information

Allele	Control
Faslpr-cg	000486 MRL/MpJ
Considerations for Choosing Controls

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.

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
002455	MRL-Faslpr.129P2(B6)-B2mtm1Unc
003234	MRL.129P2(B6)-Fastm1Osa/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
Genetic Quality Control Annual Report

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 and Inflammation Research
Autoimmunity (lupus erythematosus)
Inflammation

Mouse/Human Gene Homologs
autoimmune lymphoproliferative syndrome

References

Additional References

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Price and Supply Information

Strain Name:	MRL.CBAJms-Faslpr-cg/J
Stock Number:	002983

Price Details

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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; Email: jaxservices@jax.org. This strain is included in the Mouse Mutant Resource collection.
Licensing	See General Terms and Conditions below
Control Information	View Control Information in Strain Details.

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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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