AEG-1 KO mice lack the promoter region, exon 1 and part of intron 1 of the metadherin Mtdh (or AEG-1) gene. Metadherin 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).
Homozygous mice are viable and fertile, however, litter sizes from both homozygote and heterozgote matings are small. Aged (16 month old) mice are resistant to spontaneous tumorigenesis and aging-associated chronic inflammation. Mice treated with DEN (diethylnitrosamine) alone or in combination with phenobarbital to induce HCC do not develop tumors or lung metastasis. In the absence of MTDH (AEG-1), NFKB activation is inhibited in macrophages resulting in diminished IL6 and IL1B secretion and STAT3 activation; downstream events that are critical to tumor development. This strain may be useful for studying the tumor microenvironment in hepatocarcinogenesis.

AEG-1 KO mice lack the promoter region and exon 1 of the metadherin Mtdh (or AEG-1) gene. Metadherin is an oncogene essential to NFKB activation and is associated with the development of hepatocellular carcinoma (HCC). These mice are resistant to experimentally induced HCC and lung metastasis and may be useful for studying the tumor microenvironment in hepatocarcinogenesis.

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