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一种新型潜在抗辐射近交系小鼠品系的发育及生物学特性

The development and biological characteristics of a novel potentially radioresistant inbred mouse strain.

作者信息

Wang Qin, Du Liqing, Wang Yan, Xu Chang, Sun Zhijuan, Fu Yue, Yang Bing, Wang Yueying, Mu Chuanjie, Fan Saijun, Cai Lu, Katsube Takanori, Liu Qiang

机构信息

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine of Chinese Academy of Medical Science, Tianjin 300192, P.R. China.

Department of Cell Biology, Tianjin Medical University, Tianjin 300070, P.R. China.

出版信息

Mol Med Rep. 2017 Feb;15(2):759-767. doi: 10.3892/mmr.2016.6066. Epub 2016 Dec 22.

Abstract

The growth of biomedical research over the previous decades has been accompanied by an increase in the number, complexity and diversity of experimental animals developed as research tools, and inbred mice are some of the most widely used. However, thus far, no inbred mice have exhibited strong radioresistance for use in radiation‑damage research. To develop a radioresistant mouse model, a female Japanese outbreeding strain ICR/JCL mouse was mated with a male Chinese inbred strain 615 mouse. From the F1 generation, the mouse line was maintained by brother‑to‑sister mating. A novel mouse strain was established over >20 continuous generations and designated the Institute of Radiation Medicine-2 (IRM-2) mouse. The biological characteristics, genetic characteristics and susceptibility to radiation of these mice were determined. The IRM‑2 mice inherited traits from the parents, including strong reproductive capacity, stable physiological and biochemical indices and few differences among individuals. According to the genetic results, the IRM‑2 mice exhibited homozygosity, isogenicity and consistency, in agreement with international standards for inbred strains. Radiosensitivity studies have previously suggested that the lethal dose (LD)50 values for IRM‑2 mice were 7.17 Gy (male) and 7.5 Gy (female), resulting in a dose reduction factor value of 1.39 (male) and 1.37 (female). The mortality of IRM‑2 mice irradiated with 8 Gy total body irradiation was 15% at day 9 and 90% at day 15 after radiation. The number of nucleated cells in bone marrow, DNA content and colony‑forming unit‑spleen counts in IRM‑2 mice after exposure to γ‑ray irradiation were markedly higher than the corresponding values for the parental strains, suggesting that the IRM‑2 mice exhibit high resistance to ionizing radiation. Thus, it is suggested that this novel inbred mouse strain may be developed as an animal model of radioresistance for future use in radiation research.

摘要

在过去几十年中,生物医学研究不断发展,与此同时,作为研究工具培育出的实验动物在数量、复杂性和多样性方面都有所增加,近交系小鼠是其中使用最为广泛的一些。然而,迄今为止,尚无近交系小鼠在辐射损伤研究中表现出强大的辐射抗性。为了建立一个辐射抗性小鼠模型,将一只雌性日本远交系ICR/JCL小鼠与一只雄性中国近交系615小鼠进行交配。从F1代开始,通过兄妹交配来维持该小鼠品系。经过连续20多代培育,建立了一个新的小鼠品系,并命名为放射医学研究所2号(IRM-2)小鼠。对这些小鼠的生物学特性、遗传特征和辐射敏感性进行了测定。IRM-2小鼠继承了双亲的特性,包括强大的繁殖能力、稳定的生理生化指标以及个体间差异较小。根据遗传检测结果,IRM-2小鼠表现出纯合性、同基因性和一致性,符合近交系的国际标准。先前的放射敏感性研究表明,IRM-2小鼠的半数致死剂量(LD)50值分别为雄性7.17 Gy和雌性7.5 Gy,剂量降低系数值分别为雄性1.39和雌性1.37。全身照射8 Gy后,IRM-2小鼠在照射后第9天的死亡率为15%,第15天为90%。γ射线照射后,IRM-2小鼠骨髓中有核细胞数量、DNA含量和脾集落形成单位计数均显著高于亲本品系的相应值,表明IRM-2小鼠对电离辐射具有高度抗性。因此,建议将这种新的近交系小鼠品系开发为辐射抗性动物模型,以供未来在辐射研究中使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69e3/5364868/b6e3f3d988de/MMR-15-02-0759-g00.jpg

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