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/M...
|Allele Type||Gene Symbol||Gene Name|
|Spontaneous||Fas||Fas (TNF receptor superfamily member 6)|
|Allele Type||Gene Symbol||Gene Name|
|Spontaneous||Foxq1||forkhead box Q1|
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-Faslpr 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-Faslpr 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.)
|Allele Type||Spontaneous (Hypomorph)|
|Allele Synonym(s)||Fas-; Fas-def; MRL/lpr; Tnfrf6lpr; Tnfrsf6lpr; Tnfrsf6lpr; lpr|
|Gene Symbol and Name||Fas, Fas (TNF receptor superfamily member 6)|
|Gene Synonym(s)||AI196731; ALPS1A; APO-1; APT1; CD95; FAS1; FASTM; TNF receptor superfamily member 6; TNFR6; TNFRSF6; Tnfrsf6; Tnfrsf6; expressed sequence AI196731; lpr; lymphoproliferation|
|Strain of Origin||MRL/Mp|
|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.The Cd72c haplotype is a modifier of Faslpr-induced autoimmune disease. J:204782|
|Molecular Note||Southern blotting experiments indicated that the mutation is a genomic rearrangement within the gene, probably within the second intron. Sequencing of genomic DNA and RT-PCR products from homozygous mutant mice revealed the insertion of an early transposable element (ETn) into intron 2. RT-PCR analysis of liver and thymus mRNA showed that the presence of the ETn leads to premature termination of transcription at the long terminal repeat (LTR) of the ETn and aberrant mRNA splicing. The mutation is "leaky," however, as full-length mRNA and a longer splice product incorporating a segment of the ETn as an extra intron are detected in the thymus at low levels.|
|Allele Name||satin Jackson|
|Gene Symbol and Name||Foxq1, forkhead box Q1|
|Gene Synonym(s)||HFH-1; HFH1; HNF-3/forkhead homolog 1; HNF-3/forkhead homolog 1 like; Hfh-1; Hfh1; Hfh1; Hfh1l; Hfh1l; sa; sa; satin|
|Strain of Origin||MRL/MpJ-Faslpr/J|
|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.|
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.
At least two untested males and two untested females (two pairs) will be recovered (eight or more mice is typical).
The total number of animals provided, their gender and genotype will vary. Untested animals typically are available to
ship between 10 and 14 weeks from the date of your order. If the first recovery attempt is unsuccessful, a second recovery
will be done, extending the overall recovery time to approximately 25 weeks. Progeny testing is required to identify the
genotype of mice of this strain, as a genotyping assay is not available. This type of testing involves breeding the
recovered animals and assessing the phenotype of the offspring in order to identify animals carrying the mutation of
interest. We can perform the progeny testing for you as a service or we can ship all recovered animals to you for progeny
testing at your facility. If you perform the progeny testing, there is no guarantee that a carrier will be identified.
If we perform progeny testing as a service, additional breeding time will be required. In this case, when a male and female
(one pair) are identified that carry the mutation, they and their offspring will be shipped. Delivery time for strains
requiring progeny testing often exceeds 25 weeks and may take 12 months or more due to the difficulties in breeding some
strains. The progeny testing cost is in addition to the recovery cost and is based on the number of boxes used and the
time taken to produce the mice identified as carrying the mutation. Please Customer Service for more information
on the cost of progeny testing for a strain.
Please note that identified 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. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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