Post Mortem Study on the Effects of Routine Handling and Manipulation of Laboratory Mice

SIMPLE SUMMARY: Any routine manipulation and handling of mice for husbandry and/or experimental needs can cause physical harm. Besides being an ethical concern, trauma from manipulation and handling is a possible confounding effect on research outcomes. Specific pathologic effects of routine manipulations and handling are poorly documented and largely ignored by investigators. Our study provides a comprehensive post mortem overview of the main lesions associated with common manipulations of laboratory mice (i.e., restraint, blood drawing, and intraperitoneal injections), with an emphasis on traumatic osteoarticular changes. A total of 1000 mice were included, with 864 animals being heavily manipulated and 136 being handled for routine husbandry procedures only. Traumatic osteoarticular lesions were found in 61 heavily manipulated mice, and in a single unmanipulated mouse, showing a highly significant association between the presence of traumatic osteoarticular lesions and heavy handling of mice. We discuss the need for intentional training of research personnel on appropriate mouse handling and restraint techniques, which could help reduce the lesion frequency and the impact on animal wellbeing as well as study reproducibility. ABSTRACT: Routine handling and manipulation of laboratory mice are integral components of most preclinical studies. Any type of handling and manipulation may cause stress and result in physical harm to mice, potentially leading to unintended consequences of experimental outcomes. Nevertheless, the pathological effects of these interventions are poorly documented and assumed to have a negligible effect on experimental variables. In that context, we provide a comprehensive post mortem overview of the main pathological changes associated with routine interventions (i.e., restraint, blood drawing, and intraperitoneal injections) of laboratory mice with an emphasis on presumed traumatic osteoarticular lesions. A total of 1000 mice from various studies were included, with 864 animals being heavily manipulated and 136 being handled for routine husbandry procedures only. The most common lesions observed were associated with blood collection or intraperitoneal injections, as well as a series of traumatic osteoarticular lesions likely resulting from restraint. Osteoarticular lesions were found in 62 animals (61 heavily manipulated; 1 unmanipulated) with rib fractures and avulsion of the dens of the axis being over-represented. Histopathology and micro-CT confirmed the traumatic nature of the rib fractures. While these lesions might be unavoidable if mice are manipulated according to the current standards, intentional training of research personnel on appropriate mouse handling and restraint techniques could help reduce their frequency and the impact on animal wellbeing as well as study reproducibility.