NRSA Fellowship for Michael Orr: Acomys as a Novel Mammalian Model of Spinal Cord Injury

Less than 1% of hospitalized victims of spinal cord injury (SCI) experience full recovery by the time of discharge, which reflects an inability to regenerate injured spinal tissues and an absence of SCI therapies. Researchers commonly use regenerating, non-mammalian animal models to identify targets for inducing neural regeneration, but test regenerative therapies on non-regenerating mammals that recapitulate human SCI. Unfortunately, the phylogenetic gap between these animal models creates a significant barrier to translation. A mammalian model with enhanced regenerative capabilities would serve as a powerful tool for identifying targets for inducing a regenerative response in mammals. Spiny mice (genus Acomys) are mammals closely related to laboratory mice (genus Mus). Acomys exhibit a suite of pro-regenerative inflammatory and scarring responses to skin and ear injuries, which result in scar-free regeneration of nerves, muscle, cartilage, adipose tissue, subaceous glands, hair, and full thickness skin. Inflammation, scarring, and axon regrowth are key regulators of spinal cord injury and repair, yet none of these have been testing in Acomys. The objective of this study is to establish the utility of the spiny mouse as a novel mammalian model of SCI. To accomplish this objective, I will compare Acomys and Mus SCI responses and axon regeneration through in vitro neuron culture, functional recovery measurements, and histological analysis. The results of this study will provide insight into Acomys SCI responses and regeneration, and will establish the utility of Acomys as a novel mammalian model to identify regenerative targets following SCI.