Impact of Age, Sex, and Genetic Diversity in Murine Models of the Hematopoietic Acute Radiation Syndrome (H-ARS) and the Delayed Effects of Acute Radiation Exposure (DEARE)

Purpose of Review Malicious or accidental radiation exposure increases risk for the hematopoietic acute radiation syndrome (H-ARS) and the delayed effects of acute radiation exposure (DEARE). Radiation medical countermeasure (MCM) development relies on robust animal models reflective of all age groups and both sexes. This review details critical considerations in murine H-ARS and DEARE model development including divergent radiation responses dependent on age, sex, and genetic diversity. Recent Findings Radioresistance increases with murine age from pediatrics through geriatrics. Between sexes, radioresistance is higher in male weanlings, pubescent females, and aged males, corresponding with accelerated myelopoiesis. Jackson diversity outbred (JDO) mice resemble non-human primates in radiation response for modeling human diversity. Weanlings and JDO models exhibit less DEARE than other models. Summary Highly characterized age-, sex-, and diversity-conscious murine models of H-ARS and DEARE provide powerful and essential tools in MCM development for all radiation victims.

Automated summary

This review discusses critical factors in the development of murine models for H-ARS and DEARE, including the impact of age, sex, and genetic diversity on radiation responses. Recent studies have found that murine radioresistance increases with age, with higher resistance observed in male weanlings, pubescent females, and aged males. Jackson diversity outbred (JDO) mice and weanling models exhibit less DEARE compared to other models.