The Mechanism of Thymic Lymphomagenesis in Genetically Engineered Mouse Model

基因工程小鼠模型胸腺淋巴瘤发生机制

• 批准号: 8349382
• 负责人: Terry van Dyke
• 金额: $ 29.82万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8349382
• 关键词: Actins; Amino Acids; Atypical Lymphoproliferative Disorder; Automobile Driving; Bone Marrow Transplantation; Cells; Cytokeratin; Epithelial Cells; Family member; Genetically Engineered Mouse; Goals; Human; K-18 conjugate; Large T Antigen; Lymphoma; Lymphomagenesis; Malignant Neoplasms; Mammary gland; Mus; Pathway interactions; Prostate; Proteins; Regulation; Signal Pathway; Simian virus 40; Stromal Cells; T-Lymphocyte; Thymic epithelial cell; Time; Tissues; cytokine; lymphoblast; mouse model; neoplastic; offspring; tumorigenesis

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.

使用 T121，我们生成了一个小鼠模型，其中细胞角蛋白 (K) 18 驱动 floxed eGFP 停止 T121 表达。 K18广泛表达于简单的上皮细胞（例如前列腺管腔细胞、乳腺管腔细胞、胸腺上皮细胞等）中。一旦 K18 小鼠与 Cre 系杂交，T121 表达将直接在 K18 调节下驱动。我们已将 K18 小鼠与几种不同的 Cre 系（例如 R26CreER、b-肌动蛋白 Cre、PbCre4、PSACre 和 FSPCre）杂交。所有后代均出现非典型淋巴样增生、肿瘤前期或 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 受体小鼠中胸腺肿块形成，而在以 K18 小鼠为供体的野生型受体小鼠中没有胸腺肿块形成，表明 K18 基质有助于这些小鼠的淋巴瘤发生。