Description

Strain Information

Type Inbred Strain; Additional information on Inbred Strains. Mating System Sibling x Sibling         (Female x Male) Species laboratory mouse H2 Haplotype k Generation F137 (03-JAN-08)

Appearance
albino, unaffected
Related Genotype: a/a Tyr^c/Tyr^c Fas⁺/Fas⁺

Description
The MRL/MpJ mice are large but docile to the point that males rarely fight. They are the parent and control strain for for MRL/MpJ-Fas^lpr (Stock Nos. 000485, 006825). Despite carrying the normal Fas gene, MRL/MpJ mice also exhibit autoimmune disorders, but symptoms are manifested much later in life compared to those the MRL/MpJ-Fas^lpr mice. Starting at about three months of age, levels of circulating immune complexes rise greatly in the MRL-Fas^lpr mouse but not in the wildtype control, MRL/MpJ. Also beginning at 3 months Fas^lpr mice exhibit very severe poliferative glomerulonephritis, whereas in the MRL/MpJ controls usually only mild glomerular lesions are detected. MRL/MpJ inbred female typically die at 73 weeks of age and males die at 93 weeks. This compares to a lifespan of 17 weeks in the female and 22 weeks for males in the mouse homozygous for Fas^lpr. See MRL/MpJ-Fas^lpr (Stock No. 000485) for additional information. As a strain developed as the control for MRL/MpJ-Fas^lpr, MRL/MpJ mice are useful in the study of their comparable defects and diseases.

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 heal to 0-0.4mm in MRL/MpJ mice but are still 1.2-1.6mm in C57BL/6 mice. At 15 days post-injury C57BL/6 show a maximal closure of 30% reduction in ear hole size while MRL show 85% reduction. The process of healing in MRL/MpJ mice is faster, more complete, showed increased swelling, angiogenesis, fibroblast migration, extracellular matrix deposition, and decreased scarring and fibrosis. Additionally, hair follicles and accompanying sebaceous glands regenerate 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 shows that the MRL/MpJ healing phenotype does not readily transfer with bone marrow and remains 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%) is 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 multiple wound healing QTLs, Heal2 and Heal3 ,on MRL/MpJ chromosome 13 in the region of D13Mit115 and D13Mit129 respectively; Heal5 on MRL/MpJ chromosome 12 in the region of D12Mit233; Heal1 on chromosome 8 of C57BL/6 in the region of D8Mit211; and a highly suggestive locus on MRL/MpJ chromosome 7 in the region of D7Mit220. In crosses between MRL/MpJ x SJL/J, Masinde et al. identified 10 QTL for wound healing, confirming and extending the findings of McBrearty et al. Chromosomes 1, 3, 6, and 13 each have a single QTL with that on chromosome 13 being statistically suggestive but not significant, while chromosomes 4, 7, and 9 each have two statistically significant QTLs. (Clark et al., 1998; Leferovich et al., 2001; Kench et al., 1999; McBrearty et al., 1998; Masinde et al., 2001.)

Microarray analysis and SELDI ProteinChip analysis 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 QTLs are sexually dimorphic with Heal2, 3, 7, 8, 10, and 11 having greater effects in males and Heal4, 5, and 9 having greater effects 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 reveal= 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 1 induction 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 MRL/MpJ lymphoproliferation wildtype strain was generated from a series of crosses with strains C57BL/6J (0.3%), C3H/HeDi (12.1%), AKR/J (12.6%) and LG/J (75%) and then followed by inbeeding. The composite genome distribution is indicated in parenthesis. Current generation of inbreeding is F98+. During development of this strain, at F12, the spontaneous mutation Fas^lpr was found. MRL/MpJ-Fas^lpr (Stock Nos. 000485 and 006825) and the MRL/MpJ control are kept congenic with each other by backcrosses to the MRL/MpJ wildtype every 5-10 inbred generations.

Control Information

		This strain is a control for 000485 MRL/MpJ-Faslpr/J and 002983 MRL.CBAJms-Faslpr-cg/J.
Considerations for Choosing Controls

Additional Web Information

Genetic Quality Control Annual Report
JAX^® NOTES, Fall 2008; 511. "Healer" JAX^® Mice strain can regenerate cartilage.
JAX^® NOTES, January 1988; 432. Arthritis Models in the Mouse.

Phenotype

Phenotype Information

View Phenotypic Data

Phenotypic Data

Mouse Phenome Database
Mouse Phenome Database / SNP Facility
Festing Inbred Strain Characteristics: MRL

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

immune system phenotype

pancreas inflammation (MGI Ref ID J:1376)

• spontaneous pancreatitis in females over 22 weeks of age, with diffuse mononuclear infiltrate and destruction of acini and replacement of parenchyma with adipose, but pancreatic islets are unaffected
• incidence in females is 74% at 34-38 weeks of age; less severe in males, incidence in males is 40% at 46-50 weeks of age
• disease can be transferred with splenocytes from older females into younger, unaffected female but not male hosts, but disease can not be transferred with serum

• chronic pancreas inflammation (MGI Ref ID J:1376)

endocrine/exocrine gland phenotype

pancreas inflammation (MGI Ref ID J:1376)

• spontaneous pancreatitis in females over 22 weeks of age, with diffuse mononuclear infiltrate and destruction of acini and replacement of parenchyma with adipose, but pancreatic islets are unaffected
• incidence in females is 74% at 34-38 weeks of age; less severe in males, incidence in males is 40% at 46-50 weeks of age
• disease can be transferred with splenocytes from older females into younger, unaffected female but not male hosts, but disease can not be transferred with serum

• chronic pancreas inflammation (MGI Ref ID J:1376)

digestive/alimentary phenotype

pancreas inflammation (MGI Ref ID J:1376)

• spontaneous pancreatitis in females over 22 weeks of age, with diffuse mononuclear infiltrate and destruction of acini and replacement of parenchyma with adipose, but pancreatic islets are unaffected
• incidence in females is 74% at 34-38 weeks of age; less severe in males, incidence in males is 40% at 46-50 weeks of age
• disease can be transferred with splenocytes from older females into younger, unaffected female but not male hosts, but disease can not be transferred with serum

• chronic pancreas inflammation (MGI Ref ID J:1376)

View Research Applications

Research Applications

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

Immunology and Inflammation Research
Autoimmunity (Sjogren syndrome)
Autoimmunity (autoimmune pancreatitis and sialoadenitis)
Autoimmunity (experimentally induced rheumatoid arthritis)
Autoimmunity (lupus erythematosus)

Internal/Organ Research
Wound Healing (enhanced)

Neurobiology Research
Vestibular and Hearing Defects (Age related hearing loss, control)

Sensorineural Research
Vestibular and Hearing Defects (Age related hearing loss, control)

Genes & Alleles

Gene & Allele Information

Currently there are no related genes or alleles for this strain.

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

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]

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]  [MGI Ref ID J:109933]

Kanno H; Nose M; Itoh J; Taniguchi Y; Kyogoku M. 1992. Spontaneous development of pancreatitis in the MRL/Mp strain of mice in autoimmune mechanism. Clin Exp Immunol 89(1):68-73. [PubMed: 1352748]  [MGI Ref ID J:1376]

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]

Koh JS; Wang Z; Levine JS. 2000. Cytokine dysregulation induced by apoptotic cells is a shared characteristic of murine lupus J Immunol 165(8):4190-201. [PubMed: 11035051]  [MGI Ref ID J:65106]

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]

Masinde GL; Li X; Gu W; Davidson H; Mohan S; Baylink DJ. 2001. Identification of Wound Healing/Regeneration Quantitative Trait Loci (QTL) at Multiple Time Points that Explain Seventy Percent of Variance in (MRL/MpJ and SJL/J) Mice F(2) Population. Genome Res 11(12):2027-33. [PubMed: 11731492]  [MGI Ref ID J:73197]

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]

Perez de Lema G; Maier H; Nieto E; Vielhauer V; Luckow B; Mampaso F; Schlondorff D. 2001. Chemokine expression precedes inflammatory cell infiltration and chemokine receptor and cytokine expression during the initiation of murine lupus nephritis. J Am Soc Nephrol 12(7):1369-82. [PubMed: 11423566]  [MGI Ref ID J:109873]

Ratkay LG; Tait B; Tonzetich J; Waterfield JD. 1994. Lpr and MRL background gene involvement in the control of adjuvant enhanced arthritis in MRL-lpr mice. J Autoimmun 7(5):561-73. [PubMed: 7530961]  [MGI Ref ID J:20844]

Sakic B; Kolb B; Whishaw IQ; Gorny G; Szechtman H; Denburg JA. 2000. Immunosuppression prevents neuronal atrophy in lupus-prone mice: evidence for brain damage induced by autoimmune disease? J Neuroimmunol 111(1-2):93-101. [PubMed: 11063826]  [MGI Ref ID J:109885]

Theofilopoulos AN; Dixon FJ. 1985. Murine models of systemic lupus erythematosus. Adv Immunol 37:269-390. [PubMed: 3890479]  [MGI Ref ID J:109952]

Additional References

Jabs DA; Prendergast RA; Rorer EM; Hudson AP; Whittum-Hudson JA. 2001. Cytokines in autoimmune lacrimal gland disease in MRL/MpJ mice. Invest Ophthalmol Vis Sci 42(11):2567-71. [PubMed: 11581200]  [MGI Ref ID J:72054]

Sakic B; Szechtman H; Keffer M; Talangbayan H; Stead R; Denburg JA. 1992. A behavioral profile of autoimmune lupus-prone MRL mice. Brain Behav Immun 6(3):265-85. [PubMed: 1392101]  [MGI Ref ID J:2700]

Verhagen C; Rowshani T; Willekens B; van Haeringen NJ. 1995. Spontaneous development of corneal crystalline deposits in MRL/Mp mice. Invest Ophthalmol Vis Sci 36(2):454-61. [PubMed: 7843914]  [MGI Ref ID J:24024]

Xie C; Sharma R; Wang H; Zhou XJ; Mohan C. 2004. Strain distribution pattern of susceptibility to immune-mediated nephritis. J Immunol 172(8):5047-55. [PubMed: 15067087]  [MGI Ref ID J:122988]

Zheng QY; Johnson KR; Erway LC. 1999. Assessment of hearing in 80 inbred strains of mice by ABR threshold analyses. Hear Res 130(1-2):94-107. [PubMed: 10320101]  [MGI Ref ID J:54812]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX9

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.
Mating System	Sibling x Sibling         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply	Level 2. Up to 100 mice. Larger quantities or custom orders arranged upon request.
Supply Notes	Shipped at a specific age in weeks. Mice at a precise age in days, littermates and retired breeders are also available. Strains that must be genotyped are not available until five to seven weeks of age. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

		This strain is a control for 000485 MRL/MpJ-Faslpr/J and 002983 MRL.CBAJms-Faslpr-cg/J.
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

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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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