Overview

The Mif^P1G allele replaces the endogenous Mif gene with a mutant form of MIF that lacks a tautomerase activity (P1G-MIF). As Mif is a widely expressed cytokine and upstream regulator of the immune response by inhibiting the proapoptotic and cell cycle-regulatory function of the p53 tumor suppressor, these Mif^P1G mice may be useful for studying the structure and function of MIF, innate- and autoimmune disorders, inflammation and cancer, and tumorigenesis caused by neoangiogenesis.

Donating Investigator

Richard Bucala, Yale School of Medicine

Genetic overview

Genetic Background	Generation

Mif^tm2Gfr

Allele Type	Gene Symbol	Gene Name
Targeted	Mif	macrophage migration inhibitory factor (glycosylation-inhibiting factor)

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Research Applications

Research Tools
Immunology, Inflammation and Autoimmunity Research
Cancer Research
Apoptosis Research

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Details

Detailed Description

The Mif^P1G allele replaces the endogenous Mif gene with a mutant form of MIF that lacks the tautomerase activity (P1G-MIF). Homozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Homozygous mice have some reduction in binding to cell surface receptors compared to wildtype mice. As Mif is a widely expressed cytokine and upstream regulator of the immune response by inhibiting the proapoptotic and cell cycle-regulatory function of the p53 tumor suppressor, these Mif^P1G mice may be useful for studying the structure and function of MIF, innate- and autoimmune disorders, inflammation and cancer, and tumorigenesis caused by neoangiogenesis.

Development

The targeting vector was designed to create a proline to glycine mutation (Pro1Gly or P1G) in exon 1 of Macrophage migration-inhibitory factor (Mif), and to insert a self-excising loxP-flanked cassette (itself containing a neomycin resistance (Neo) gene and a testes-specific angiotensin-converting enzyme promoter-driven Cre recombinase gene (tACE-Cre)). The construct was electroporated into C57BL/6-derived Bruce-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into BALB/c blastocysts and the donating investigator reported that the resulting chimeric males were bred to C57BL/6Crl females (see SNP note below). Mice heterozygous for this Mif^P1G allele were bred together to generate homozygotes. Upon arrival mice at the MMRRC at The Jackson Laboratory these mice were bred to C57BL/6J inbred mice for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at the MMRRC at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 1 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to the MMRRC at The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Fingerle-Rowson G; Kaleswarapu DR; Schlander C; Kabgani N; Brocks T; Reinart N; Busch R; Schutz A; Lue H; Du X; Liu A; Xiong H; Chen Y; Nemajerova A; Hallek M; Bernhagen J; Leng L; Bucala R. 2009. A tautomerase-null macrophage migration-inhibitory factor (MIF) gene knock-in mouse model reveals that protein interactions and not enzymatic activity mediate MIF-dependent growth regulation. Mol Cell Biol 29(7):1922-32PubMed: 19188446 MGI: J:147772

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Genetics

Mif^tm2Gfr

Allele Symbol: Mif^tm2Gfr

Allele Name	targeted mutation 2, G Fingerle-Rowson
Allele Type	Targeted
Allele Synonym(s)	mif^P1G
Gene Symbol and Name	Mif, macrophage migration inhibitory factor (glycosylation-inhibiting factor)
Gene Synonym(s)
Promoter	Mif, macrophage migration inhibitory factor (glycosylation-inhibiting factor), mouse, laboratory
Strain of Origin	B6.Cg-Thy1^a
Chromosome	10
Molecular Note	Nucleotide substitutions (CCT->GGC) results in the amino acid substitution of glycine for proline at position 1 (P1G). A self-excising floxed neo cassette was inserted downstream of exon 3 and successfully self-excised following germ line passage. Enzymatic activity of the protein is absent.
Mutations Made By	Gunter Fingerle-Rowson, University Hospital Cologne

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Apoptosis Research
- Immunology, Inflammation and Autoimmunity Research
  - Macrophage Deficiency
- Cancer Research
  - tumor immunology
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
- Autoimmunity
Cancer Research
- Growth Factors/Receptors/Cytokines
Apoptosis Research
- Endogenous Regulators

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Mif^tm2Gfr/Mif^tm2Gfr
C57BL/6-Mif

cellular phenotype

decreased fibroblast proliferation
- mouse embryonic fibroblasts exhibit reduced proliferation compared to wild-type cells that is not as severe as in Mif^tm1Gfr homozygous cells
- malignant mouse embryonic fibroblasts exhibit a modest proliferation defect compared to wild-type cells

homeostasis/metabolism phenotype

increased incidence of tumors by chemical induction
- benzo[alpha]pyrene-treated mice develop more benign tumors relative to malignant tumors than in similarly treated wild-type mice but not as much as in Mif^tm1Gfr homozygotes
- mice treated with benzo[alpha]pyrene-induced develop more skin tumors compared to similarly treated wild-type mice

neoplasm

increased incidence of tumors by chemical induction
- benzo[alpha]pyrene-treated mice develop more benign tumors relative to malignant tumors than in similarly treated wild-type mice but not as much as in Mif^tm1Gfr homozygotes
- mice treated with benzo[alpha]pyrene-induced develop more skin tumors compared to similarly treated wild-type mice

References

Fingerle-Rowson G; Kaleswarapu DR; Schlander C; Kabgani N; Brocks T; Reinart N; Busch R; Schutz A; Lue H; Du X; Liu A; Xiong H; Chen Y; Nemajerova A; Hallek M; Bernhagen J; Leng L; Bucala R. 2009. A tautomerase-null macrophage migration-inhibitory factor (MIF) gene knock-in mouse model reveals that protein interactions and not enzymatic activity mediate MIF-dependent growth regulation. Mol Cell Biol 29(7):1922-32PubMed: 19188446 MGI: J:147772

Additional - Mif^tm2Gfr related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Mif
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the C57BL/6-Mif^tm2Gfr/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32057 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Miftm2Gfr

Allele Symbol: Miftm2Gfr

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Miftm2Gfr/Miftm2GfrC57BL/6-Mif

cellular phenotype

homeostasis/metabolism phenotype

neoplasm

References

Additional - Miftm2Gfr related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Mif^tm2Gfr

Allele Symbol: Mif^tm2Gfr

Genotype: Mif^tm2Gfr/Mif^tm2Gfr
C57BL/6-Mif

Additional - Mif^tm2Gfr related