[HUP98-HOXA9 transgenic mice are susceptible to N-ethyl-N-nitrosourea stimulation in leukemogenesis].

Objective In order to investigate the leukemogenic potential of NUP98 HOXA9 fusion gene in vivo. Methods Molecular cloning technology was used to construct NUP98 HOXA9 transgenic plasmid and NUP98 HOXA9 transgenic mice were generated.The genotype and phenotype of the NUP98 HOXA9 transgenic mice were analyzed by PCR, RT PCR and colony forming assay. The effect of N ethyl N nitrosourea (ENU) stimulation on the transgenic mice was analyzed by peripheral blood count, bone marrow (BM) cells morphology pathological examination. Results The transgenic expression was detected in 5 independent lines of NUP98 HOXA9 transgenic mice, but no expected phenotypes was found in 2 year follow up. Upon ENU stimulation, 2 of 10 transgenic mice developed myeloid leukemia, suggesting that NUP98 HOXA9 transgenic mice have increased susceptibility to ENU mutagenesis in leukemogenesis.Conclusion The fusion gene expressed in BM cells of NUP98 HOXA9 transgenic mice. It seems that the expression of the fusion gene is insufficient to trigger leukemogenesis. However, the increased susceptibility to ENU mutagenesis suggests that NUP98 HOXA9 fusion gene might play a potential role in leukemogenesis.