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General Terms and Conditions

Former Name	MRL/MpJ-Faslpr-Foxq1sa-J/J    (Changed: 28-MAR-06 )
	MRL/MpJ-Tnfrsf6lpr-Foxq1sa-J/J    (Changed: 26-JAN-05 )
	MRL/MpJ-Tnfrsf6lpr-saJ    (Changed: 15-DEC-04 )
Genes & Alleles	Fas;   Faslpr;   Foxq1;   Foxq1sa-J;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Coisogenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Spontaneous Mutation Mating System Homozygote x Heterozygote         (Female x Male) Mating System Heterozygote x Homozygote         (Female x Male) Species laboratory mouse H2 Haplotype k Generation N1F30 (06-DEC-07)

Appearance
albino, silky coat, affected
Related Genotype: a/a Tyr^c/Tyr^c Foxq1^sa-J/Foxq1^sa-J Fas^lpr/Fas^lpr

albino, normal coat, affected
Related Genotype: a/a Tyr^c/Tyr^c Foxq1^sa-J/+ Fas^lpr/Fas^lpr

Strain Description
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-Fas^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-Fas^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 trans forming growth factor beta 1 production. (Kench et al., 1999.)

Mammalian Phenotype Terms assigned by genotype Foxq1sa-J/Foxq1sa-J         MRL/MpJ-Faslpr/J skin/coat/nails phenotype shiny fur (MGI Ref ID J:78121) mice have silky coats with a high sheen

Gene & Allele Details

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. The resemblance has led to extensive use of Faslpr mice in attemptsto 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.
Molecular Note		Southern blotting experiments indicated that the mutation is a genomic rearrangement within the gene, probably within intron 2. [MGI Ref ID J:1181] [MGI Ref ID J:14206] [MGI Ref ID J:14503] [MGI Ref ID J:15429] [MGI Ref ID J:4166] [MGI Ref ID J:4342] [MGI Ref ID J:72675] [MGI Ref ID J:92470]
Allele Symbol		Foxq1sa-J
Allele Name		satin Jackson
Strain of Origin		MRL/MpJ-Faslpr/J
Gene Symbol and Name		Foxq1, forkhead box Q1
Chromosome		13
Gene Common Name(s)		HFH-1; HFH1; HNF-3/forkhead homolog 1; HNF-3/forkhead homolog 1 like; Hfh1; Hfh1l; sa; satin;
Molecular Note		A spontaneous mutant identified at The Jackson Laboratory. A complementation test with Foxq1sa demonstrated that the mutant was a new allele at the Foxq1 locus.

Control Information

Allele	Control
Foxq1sa-J	Heterozygote from the colony
Considerations for Choosing Controls

Genotyping Protocols

Fas^lpr

Colony Maintenance

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

Related Strains

Strains carrying   Fas^lpr allele

000482	B6.MRL-Faslpr/J
000480	C3.MRL-Faslpr/J
002455	MRL-Faslpr.129P2(B6)-B2mtm1Unc
006825	MRL/MpJ-Faslpr/2J
000485	MRL/MpJ-Faslpr/J
004519	NOD.MRL(C3)-Faslpr/DoiJ
004922	NOD.MRL-Faslpr/Dvs

View Strains carrying   Fas^lpr     (7 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 Foxq1

000269

SB/LeJ

View Strains carrying other alleles of Foxq1     (1 strain)

Animal Health Reports

Room Number           A1

Research Applications

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

Fas^lpr related

Apoptosis 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

Foxq1^sa-J related

Dermatology Research
Skin and Hair Texture Defects

References

Selected Reference(s)

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]

Kench JA; Russell DM; Fadok VA; Young SK; Worthen GS; Jones-Carson J; Henson JE; Henson PM; Nemazee D. 1999. Aberrant wound healing and TGF-beta production in the autoimmune-prone MRL/+ mouse. Clin Immunol 92(3):300-10. [PubMed: 10479535]  [MGI Ref ID J:57718]

Leferovich JM; Bedelbaeva K; Samulewicz S; Zhang XM; Zwas D; Lankford EB; Heber-Katz E. 2001. Heart regeneration in adult MRL mice. Proc Natl Acad Sci U S A 98(17):9830-5. [PubMed: 11493713]  [MGI Ref ID J:109867]

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]

McBrearty BA; Clark LD; Zhang XM; Blankenhorn EP; Heber-Katz E. 1998. Genetic analysis of a mammalian wound-healing trait. Proc Natl Acad Sci U S A 95(20):11792-7. [PubMed: 9751744]  [MGI Ref ID J:50111]

Additional References

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Price and Supply Information

Strain Name:	MRL/MpJ Faslpr-Foxq1sa-J/J
Stock Number:	003896

Price Details

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Supply Details

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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View JAX^® Mice & Services Conditions 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.

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