Cho Kyu-Hyuk, Cho Jae-Woo, Song Chang-Woo
Department of Research & Development, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, P.O BOX 123, Yuseong, Daejeon, 305-343 Korea.
Toxicol Res. 2008 Mar;24(1):59-68. doi: 10.5487/TR.2008.24.1.059. Epub 2008 Mar 1.
N-ethyl-N-nitrosoures (ENU) is effective in inducing hypermorphic mutation as well as hypomorphic and antimorphic mutations. Therefore, this mutagen is used to the production of mutant in the mice. In order to perform an effective ENU mutagenesis using BALB/cAnN mice, determination of optimal dosage and dosage regimen of ENU is necessary. And this study tried to develop a suitable screening method and searched for novel and various mutants as model animals in phenotypedriven ENU mutagenesis. We have carried out dosage regimen for mutagenizing dose of 200 mg/kg ENU in the BALB/c mice. Total screened mice were 30,133. As the results of Esaki and Cho's Phenotype Screening, we got 2,516 phenotypic and behavior abnormalities in G, G and G mice. One hundred thirty five G1 phenodeviants were tested for inheritance and 16 dominant mutants were discovered. Forty two recessive mutants were also found in tested 201 micropedigrees. Early-onset mutant mice included the dysmorphology of face, eye, tail, limb, skin, and foot and abnormal behavior like circling, swimming, head tossing, stiff-walking, high cholesterol level, and tremor etc. In this study we could effectively screen G3 recessive mutants. The frequent and concise early-onset screening before weaning will be available for ENU mutagenesis.
N-乙基-N-亚硝基脲（ENU）在诱导超形态突变以及亚形态和反形态突变方面很有效。因此，这种诱变剂被用于在小鼠中产生突变体。为了使用BALB/cAnN小鼠进行有效的ENU诱变，确定ENU的最佳剂量和给药方案是必要的。并且本研究试图开发一种合适的筛选方法，并在表型驱动的ENU诱变中寻找作为模型动物的新型和各种突变体。我们已经对BALB/c小鼠进行了200 mg/kg ENU诱变剂量的给药方案。总共筛选了30133只小鼠。作为Esaki和Cho的表型筛选结果，我们在G1、G2和G3小鼠中获得了2516种表型和行为异常。对135只G1表型异常小鼠进行了遗传测试，发现了16个显性突变体。在测试的201个小家系中还发现了42个隐性突变体。早发性突变小鼠包括面部、眼睛、尾巴、四肢、皮肤和足部的畸形以及诸如转圈、游泳、甩头、僵硬行走、高胆固醇水平和震颤等异常行为。在本研究中，我们可以有效地筛选G3隐性突变体。断奶前频繁且简洁的早发性筛选将可用于ENU诱变。
