The Mechanism of Thymic Lymphomagenesis in Genetically Engineered Mouse Model

使用T121，我们产生了小鼠模型，其中细胞角蛋白（K）18驱动floxed eGFP终止T121表达。K18广泛表达于单纯上皮细胞（如前列腺腔细胞、乳腺腔细胞、胸腺上皮细胞等）。一旦K18小鼠与Cre系杂交，T121表达将直接在K18调控下驱动。我们已经将K18小鼠与几种不同的Cre系（例如R26 CreER、b-肌动蛋白Cre、PbCre 4、PSACre和FSPCre）杂交。所有后代均发生非典型淋巴样增生、肿瘤前或T细胞淋巴母细胞淋巴瘤。骨髓移植研究表明，仅在以野生型小鼠为供体的K18受体小鼠中产生胸腺肿块，而以K18小鼠为供体的野生型受体小鼠中未产生胸腺肿块，表明K18基质有助于这些小鼠中的淋巴瘤发生。

Using T121, we generated a mouse model, in which cytokeratin (K) 18 drives floxed eGFP stop T121 expression. K18 is expressed widely in simple epithelial cells (e.g. prostate luminal cells, mammary gland luminal cells, thymic epithelial cells, etc). Once K18 mouse is crossed to a Cre line, T121 expression will be driving directly under K18 regulation. We have crossed K18 mouse to several different Cre lines (e.g. R26CreER, b-actin Cre, PbCre4, PSACre, and FSPCre). All offspring developed atypical lymphoid hyperplasia, pre-neoplastic, or T-cell lymphoblasts lymphoma. Bone marrow transplantation study showed that thymic mass was developed only in K18 recipient mice with wildtype mice as donors, and no thymic mass developed in wildtype recipient mice with K18 mice as donors, suggesting K18 stroma contribute to the lymphomagenesis in these mice.