C57BL/6-Mif^tm2Gfr/Mmjax

Stock number: 012304
Research areas: Apoptosis Research, Cancer Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

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.

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.

Allele

Symbol: Mif^tm2Gfr
Name: targeted mutation 2, G Fingerle-Rowson
MGI accession ID: MGI:3842525
Generation method: Targeted
Marker symbol: Mif
Marker name: macrophage migration inhibitory factor (glycosylation-inhibiting factor)
Chromosome: 10
Strain of origin: B6.Cg-Thy1^a
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.