[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.


CONCLUSIONS
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.
Lu
Shun-yuan
SY
Lab of Medical & Molecular Genetics, Department of Medical Genetics, State Key Lab of Medical Genomics, Rui-jin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Gu
Ming-min
MM
Wang
Yang
Y
Tan
Yi
Y
Sun
Yue-ping
YP
Wang
Long
L
Kong
Hui
H
Lu
Zhen-yu
ZY
Wang
Zhu-gang
ZG
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005038:Ethylnitrosourea; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D005838:Genotype; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D028861:Nuclear Pore Complex Proteins / Q000096:biosynthesis / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics*; D010641:Phenotype; D010957:Plasmids; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D018398:Homeodomain Proteins; C400441:NUP98-HOXA9 fusion protein, human; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; D005038:Ethylnitrosourea