Ovarian teratomas associated with the insertion of an imprinted transgene

Abstract

Ovarian teratomas are tumors that arise from female germ cells and are often a mixture of immature embryonal carcinoma cells and mature embryonic cells. Tissues derived from all three primary embryonic lineages (ectoderm, mesoderm, and endoderm) are typically found in the mature elements of a teratoma. In the case of the transgenic mouse line TG.KD, created with an imprinted transgene construct, malignant ovarian teratomas of a mixed germ cell tumor morphology occur in 15-20% of hemizygous female carriers of the transgene. The tumors frequently metastasize and can result in death of the mouse. Genetic analysis indicates that the tumors are associated with the transgenes integration site. Inbred FVB/N and female mice of other transgenic lines, also created in the inbred FVB/N strain with the same DNA construct as TG.KD, do not develop teratomas. In addition to teratomas, the integration of the transgene on Chromosome (Chr) 8 is associated with a perinatal lethality in homozygous transgenic carriers. The hemizygous genotypes of the teratomas suggest that they arise from early germ cells, prior to the completion of meiosis I.