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

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.

Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer

“…11a ). In other cell lines, STAT3 localization was modulated only by parasite Type I ROP16 127 – 129 . This is similar, but not identical, to the nuclear translocation of STAT3 in our human neuronal stem cells, which was increased most, but not exclusively, by the Type I strain.…”

A preclinical model to investigate normal tissue damage following fractionated radiotherapy to the head and neck

“…Compared to other mouse strains, C57BL/6 is relatively radioresistant (28-30) and is therefore a suitable strain for studying both early and late radiation-induced effects in the same model, as the mice will tolerate high doses of radiation. It is also the most widespread substrain used for studying genetically engineered mice (31) and has been recommended for studies with radioprotectors and mitigators (32). It is well known that inbred mice are roughly half as sensitive to radiation as humans (30).…”

The Effects of Melatonin Administration on Intestinal Injury Caused by Abdominal Irradiation from Mice

“…The data suggest that melatonin may alleviate radiation-caused damage on hematopoietic cells by promoting antioxidant activity. It has been well established that mice irradiated with fatal doses of radiation that survive depend on the restoration of the hematopoietic system [ 15 ]. Therefore, the survival rate and the body weight of the melatonin-treated mice prior to radiation was improved in the study.…”

“…To determine the effect of melatonin on innate immunity, we examined the change in immune organs and immune cells following melatonin treatment. The spleen is the largest lymphoid organ in the human body and the colony-forming ability of the spleen was used to evaluate the immune function following exposure to high doses of IR [ 15 ]. We found that melatonin administration resulted in an increase in the CFU-S and spleen/thymus coefficient.…”