Characterization and Etiology of Swollen Muzzles in Irradiated Mice

Garrett, Joy; Sampson, Carol H.; Plett, P. Artur; Crisler, Robin; Parker, Jeffrey; Venezia, Richard A.; Chua, Hui Lin; Hickman, Debra L.; Booth, Catherine; MacVittie, Thomas J.; Orschell, Christie M.; Dynlacht, Joseph R.

doi:10.1667/rr14724.1

Cited by 13 publications

(7 citation statements)

References 21 publications

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“…Few published studies were identified in the literature that specifically compared the effect of radiation on organisms acquired from different vendors or barriers, although there are indications that this variable can lead to different outcomes across laboratories ( Garrett et al 2019 ). In one study, when mice from two different vendors (both inbred and outbred mice) were irradiated at several different radiation dose levels, there was a significant different in sensitivity between the two companies, especially for the outbred mouse strain ( Ryu et al, 2016 ).…”

Section: Animal Selectionmentioning

confidence: 99%

“…cirprofloxacin) are also known mitigators ( Fukumoto et al 2014 ). Acquiring mice from facilities with more stringent barrier procedures could also reduce swollen muzzle syndrome, as well as monitoring health reports from these particular facilities ( Garrett et al 2019 ). Despite these data and the attractiveness of modeling the human experience, researchers may also want to consider antimicrobial stewardship when deciding whether to routinely provide antibiotics in all radiation studies.…”

Section: Medical Management and MCM Testingmentioning

confidence: 99%

“…If these face the source of radiation, it may lead to sensitivity of the exposed area. For example, some instances of the ‘swollen muzzle’ syndrome (discussed above) ( Garrett et al 2019 ) could be due to the presence of air holes at the top of a radiation pie jig setup, where the radiation exposure comes from above. This geometry could allow the animals to poke their noses outside of the enclosure, leading to a higher than anticipated radiation exposure to that area (personal communication, Michelle Lambert, Children’s Hospital of Philadelphia, 2017).…”

Section: Radiation Attributesmentioning

confidence: 99%

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Study logistics that can impact medical countermeasure efficacy testing in mouse models of radiation injury

DiCarlo

Horta

Rios

et al. 2020

International Journal of Radiation Biology

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Purpose: To address confounding issues that have been noted in planning and conducting studies to identify biomarkers of radiation injury, develop animal models to simulate these injuries, and test potential medical countermeasures to mitigate/treat damage caused by radiation exposure. Methods: The authors completed an intensive literature search to address several key areas that should be considered before embarking on studies to assess efficacy of medical countermeasure approaches in mouse models of radiation injury. These considerations include: (1) study variables; (2) animal selection criteria; (3) animal husbandry; (4) medical management; and (5) radiation attributes. Results: It is important to select mouse strains that are capable of responding to the selected radiation exposure (e.g. genetic predispositions might influence radiation sensitivity and proclivity to certain phenotypes of radiation injury), and that also react in a manner similar to humans. Gender, vendor, age, weight, and even seasonal variations are all important factors to consider. In addition, the housing and husbandry of the animals (i.e. feed, environment, handling, time of day of irradiation and animal restraint), as well as the medical management provided (e.g. use of acidified water, antibiotics, routes of administration of drugs, consideration of animal numbers, and euthanasia criteria) should all be addressed. Finally, the radiation exposure itself should be tightly controlled, by ensuring a full understanding and reporting of the radiation source, dose and dose rate, shielding and geometry of exposure, while also providing accurate dosimetry. It is important to understand how all the above factors contribute to the development of radiation dose response curves for a given animal facility with a well-defined murine model. Conclusions: Many potential confounders that could impact the outcomes of studies to assess efficacy of a medical countermeasure for radiation-induced injuries are addressed, and recommendations are made to assist investigators in carrying out research that is robust, reproducible, and accurate.

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Section: Animal Selectionmentioning

confidence: 99%

Section: Medical Management and MCM Testingmentioning

confidence: 99%

Section: Radiation Attributesmentioning

confidence: 99%

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Study logistics that can impact medical countermeasure efficacy testing in mouse models of radiation injury

DiCarlo

Horta

Rios

et al. 2020

International Journal of Radiation Biology

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“…The authors have previously developed a well-characterized murine model of H-ARS and DEARE in young adult C57BL/6 mice, and have used this model to study mechanisms and efficacy of MCM against radiation for licensure and treatment strategies (Plett et al 2012, Shakhov et al 2012, Hoggatt et al 2013, Garrett et al 2014, Unthank et al 2015, Fish et al 2016, Dynlacht et al 2017, Garrett et al 2019, Jones et al 2019, Unthank et al 2019. Herein, the authors have characterized the prolonged immunosuppression at all levels of lymphocyte development in these acute and chronic radiation models.…”

Section: Introductionmentioning

confidence: 99%

Immune Reconstitution and Thymic Involution in the Acute and Delayed Hematopoietic Radiation Syndromes

Plett

Chua

et al. 2020

Health Physics

Self Cite

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Lymphoid lineage recovery and involution after exposure to potentially lethal doses of ionizing radiation have not been well defined, especially the long-term effects in aged survivors and with regard to male / female differences. To examine these questions, male and female C57BL/6 mice were exposed to lethal radiation at 12 weeks of age in a model of the Hematopoietic-Acute Radiation Syndrome, and bone marrow, thymus, spleen and peripheral blood examined up to 24 months of age for the lymphopoietic Delayed Effects of Acute Radiation Exposure. Aged mice showed myeloid skewing and incomplete lymphocyte recovery in all lymphoid tissues. Spleen and peripheral blood both exhibited a mono-phasic recovery pattern while thymus demonstrated a biphasic pattern. Naïve T cells in blood and spleen and all subsets of thymocytes were decreased in aged irradiated mice compared to age-matched non-irradiated controls. Of interest, irradiated males experienced significantly improved reconstitution of thymocyte subsets and peripheral blood elements compared to females. Bone marrow from aged irradiated survivors was significantly deficient in the primitive lymphoid-primed multipotent progenitors and common lymphoid progenitors, which were only 8-10% of levels in aged-matched non-irradiated controls. Taken together, these analyses define significant age-and sex-related deficiencies at all levels of lymphopoiesis throughout the lifespan of survivors of the Hematopoietic-Acute Radiation Syndrome, and may provide a murine model suitable for assessing the efficacy of potential medical countermeasures and therapeutic strategies to alleviate the severe immune suppression that occurs after radiation exposure.

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“…As mice age, like humans, health issues and phenotypic changes begin to manifest and variability in experimental endpoints increases, necessitating the need for larger group sizes for sufficient statistical power. For example, mice of similar strains have been shown to exhibit significantly different life spans [ 215 , 216 ] and radiation sensitivities when aged (Orschell, unpublished data), as well as differing susceptibilities to radiation-induced swollen muzzle syndrome [ 217 ], all depending on the vendor from which they were sourced. Mice from different vendors have also been shown to possess different fecal microbiota [ 218 ], which may contribute to vendor-specific phenotypic differences.…”

Section: F) Apoptosis Autophagy Radiation and A Role For The Sirtumentioning

confidence: 99%

Fate of Hematopoiesis During Aging. What Do We Really Know, and What are its Implications?

Broxmeyer

Liu

Kapur

et al. 2020

Stem Cell Rev and Rep

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There is an ongoing shift in demographics such that older persons will outnumber young persons in the coming years, and with it age-associated tissue attrition and increased diseases and disorders. There has been increased information on the association of the aging process with dysregulation of hematopoietic stem (HSC) and progenitor (HPC) cells, and hematopoiesis. This review provides an extensive up-to date summary on the literature of aged hematopoiesis and HSCs placed in context of potential artifacts of the collection and processing procedure, that may not be totally representative of the status of HSCs in their in vivo bone marrow microenvironment, and what the implications of this are for understanding aged hematopoiesis. This review covers a number of interactive areas, many of which have not been adequately explored. There are still many unknowns and mechanistic insights to be elucidated to better understand effects of aging on the hematopoietic system, efforts that will take multidisciplinary approaches, and that could lead to means to ameliorate at least some of the dysregulation of HSCs and HPCs associated with the aging process. Graphical Abstract

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Characterization and Etiology of Swollen Muzzles in Irradiated Mice

Cited by 13 publications

References 21 publications

Study logistics that can impact medical countermeasure efficacy testing in mouse models of radiation injury

Study logistics that can impact medical countermeasure efficacy testing in mouse models of radiation injury

Immune Reconstitution and Thymic Involution in the Acute and Delayed Hematopoietic Radiation Syndromes

Fate of Hematopoiesis During Aging. What Do We Really Know, and What are its Implications?

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