Expression of a Pim-1 transgene accelerates lymphoproliferation and inhibits apoptosis in lpr/lpr mice

作者: T. Moroy , A. Grzeschiczek , S. Petzold , K. U. Hartmann

DOI: 10.1073/PNAS.90.22.10734

关键词:

摘要: Transgenic mice expressing the Pim-1 kinase are predisposed to develop T-cell lymphomas with a long latency period of about 7-9 months. However, exact functional basis oncogenic activity remains obscure. C57BL/6 homozygous for lpr mutation well-described lymphoproliferative syndrome at 26-30 weeks age. This is characterized mainly by accumulation abnormal T cells in lymph nodes because lack Fas receptor-induced apoptosis. We find that backcross E mu-Pim-1 transgenics (mice transgene carries mouse gene under transcriptional control immunoglobulin heavy chain enhancer mu) into lpr/lpr results strong acceleration lymphoproliferation and dramatic enlargement nodes. In addition, we show here cultured node from rescued rapid apoptosis normally occurs nontransgenic vitro. also present evidence CD4+/CD8+ double-positive thymocytes sensitive dexamethasone-induced apoptosis, although receptor. contrast, animals considerable protection These can strongly accelerate through inhibition thereby provide first insight Pim-1.

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