STOCK Mtdh^tm1.1Dsar/J

Stock number: 029423
Product name: AEG-1 CKO
Research areas: Cancer Research, Research Tools

Description

These AEG-1 conditional KO mutant mice possess loxP sites flanking the promoter region and exon 1 of the metadherin (Mtdh or AEG-1) gene, an oncogene involved in NFKB activation and associated with hepatocellular carcinoma. This strain may be useful for studying the tumor microenvironment in hepatocarcinogenesis.

Detailed description

These AEG-1 conditional KO (CKO) mutant mice possess loxP sites flanking the promoter region and exon 1 of the metadherin (Mtdh or AEG-1) gene. Mtdh is an oncogene essential to NFKB activation; overexpression of MTDH is observed in all cancers and correlates with aggressive metastasis and poor prognosis. In particular, activation of Mtdh is associated with the development of hepatocellular carcinoma (HCC). Mice that are homozygous for this allele are viable, fertile, and normal in size. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 1 deleted in the cre-expressing tissues. This strain may be useful for studying the tumor microenvironment in hepatocarcinogenesis.

When bred to mice carrying Tg(EIIa-cre)C5379Lmgd (Stock No. 003724), Cre-mediated recombination results in resistance to induced hepatocarcinogenesis and lung metastasis.

Development

The targeting vector contains a loxP site upstream of the promoter region and a loxP-flanked neomycin cassette downstream of exon 1. The targeting vector was introduced to (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. The neomycin resistance cassette was subsequently excised by crossing to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J mice, leaving exon 1 flanked by loxP sites. This strain was backcrossed to C57BL/6 for 6 generations by the donating investigator (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

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 rederived living colony at The Jackson Laboratory Repository. Two of the 43 markers throughout the genome were segregating, suggesting an incomplete backcross. Also, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Allele

Symbol: Mtdh^tm1.1Dsar
Name: targeted mutation 1.1, Devanand Sarkar
MGI accession ID: MGI:5662532
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: AEG-1 CKO
Marker symbol: Mtdh
Marker name: metadherin
Marker synonyms: 2610103J23Rik; 3D3; 3D3/Lyric; AEG1; AEG-1; D8Bwg1112e; Lyric; LYRIC/3D3
Chromosome: 15
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A loxP site was inserted upstream of exon 1 and a floxed pgk-neo cassette was inserted downstream of exon 1 via homologous recombination. Cre mediated recombination removed the neo cassette.