C57BL/6-Map2k1^tm1.1Oaw/J

Stock number: 040482
Product name: MEK1^E102_I103del cKI
Research areas: Cancer Research, Cell Biology Research, Research Tools

Description

MEK1^E102_I103del mice harbor a Cre-inducible mutation in exon 3 of the mitogen-activated protein kinase kinase 1 (Map2k1) gene, the mutation results in loss of two amino acids (E102_I103del). These mice may be useful for studying histiocytic cancers.

Detailed description

The Map2k1 gene encodes a component of the MAP kinase signal transduction pathway, also referred to as MEK1. These MEK1^E102_I103del mice harbor a Cre-inducible mutation in exon 3 of the mitogen-activated protein kinase kinase 1 (Map2k1) gene, the mutation results in loss of two amino acids (MEK1 E102_I103del). This is one of the most expressed MEK1 mutations found in human histiocytic tumors and notably resistant to RAS inhibitors. After Cre-mediated recombination, wildtype exon 3 will be excised and the exon 3 harboring the E102_I103del mutations is expressed in cre-expressing tissues.

Heterozygous mice are viable and fertile with no overt phenotype. The donating investigator notes that homozygous mice are not produced from heterozygous x heterozygous matings. The expression of wildtype Map2k1 prior to Cre-recombination has not been evaluated to date (April 2025). When MEK1^E102_I103del mice are bred to an Mx1-Cre mouse line, the resulting Mx1-Cre;MEK1^E102_I103del progeny had a medial survival of ~59 days of age, with development of red cutaneous lesions as well as leukopenia, macrocytic anemia, and thrombocytopenia. These mice may be useful for studying histiocytic cancers.

Development

The MEK1^E102_I103del targeting vector was designed to express a loxP-flanked mutant exon 3, carrying the E102_I103del mutation, of the mitogen-activated protein kinase kinase 1 (Map2k1) gene. The targeting construct consisted of an initial loxP site, wildtype exon 3 sequence, an SV40 polyA sequence, an FRT-flanked neomycin selection cassette, a second loxP site, followed by an inverted mutant exon 3 sequence (c.303_308del; GGAGAT) and a third loxP site in opposite orientation of the second loxP site. The construct was electroporated into C57BL/6-derived iTL BF1 embryonic stem (ES) cells (C57BL/6 FLP), which express FLP recombinase vector to remove the selection cassette. Correctly targeted ES cells were injected into BALB/c blastocysts. Chimeric mice were bred to C57BL/6J mice to confirm germline transmission. Resulting MEK1^E102_I103del mice were then backcrossed to C57BL/6J mice for at least 14 generations by the donating laboratory (see SNP note below). Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J (Stock No. 000664) oocytes.

In 2025, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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 males sent to The Jackson Laboratory Repository. All 4 of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating, including the rd8 recessive mutation associated with retinal degeneration on Chromosome 1 within the Crb1 locus. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Map2k1^tm1.1Oaw
Name: targeted mutation 1.1, Omar Abdel-Wahab
MGI accession ID: MGI:8209249
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Marker symbol: Map2k1
Marker name: mitogen-activated protein kinase kinase 1
Marker synonyms: CFC3; MAP kinase kinase 1; MAPKK1; MEK1; MEL; MKK1; Prkmk1
Chromosome: 9
Strain of origin: C57BL/6NTac
Molecular note: The targeting vector was designed to express a loxP-flanked mutant exon 3, carrying the E102_I103del mutation, of the mitogen-activated protein kinase kinase 1 (Map2k1) gene. The targeting construct consisted of an initial loxP site, wildtype exon 3 sequence, an SV40 polyA sequence, an FRT-flanked neomycin selection cassette, a second loxP site, followed by an inverted mutant exon 3 sequence (c.303_308del; GGAGAT) and a third loxP site in opposite orientation of the second loxP site. FLP recombinase removed the selection cassette.