Malcolm Maden

Midventral skin glands secrete odors that mediate social contexts and are commonly found in rodents in the Cricetidae family rather than those in the Muridae family. African spiny mice ( Acomys cahirinus ) are rodents in the family Muridae known for their remarkable regenerative abilities, menstruation, tail osteoderms, and unique social behaviors, including cooperative breeding, communal parenting, and low aggression. They are also related to gerbils ( Meriones ), which are among the few murids that lack preputial glands and instead scent‐mark with midventral glands. Acomys also lack preputial glands, but whether they have midventral glands is less well known. Here, we determined that Acomys have midventral glands near the umbilicus. As in Meriones , male Acomys had larger midventral glands that were visible after depilation. Immunohistochemistry showed that midventral glands in both sexes were positive for androgen receptors, suggesting they may be under androgen control. This investigation provides basic information on the presence, location, structure, and sexual dimorphism of the midventral glands in Acomys , providing a morphological baseline for comparative studies of social signaling across the Muridae family.

The African spiny mouse, Acomys cahirinus, is an unusual mammalian model of regeneration that exhibits reduced fibrotic repair compared with Mus musculus. To determine whether this species-level difference is reflected in neural explant architecture, we compared adult dorsal root ganglion (DRG) explants from Acomys and Mus under identical in vitro conditions. Instead of focusing solely on neurite length, we examined the spatial organization of the outgrowth field and its relationship to non-neuronal cellular architecture over time in culture. Both species exhibited neurite extension; however, their outgrowth patterns differed markedly. Acomys explants frequently developed a compact, radially organized scaffold-like phenotype characterized by aligned vimentin-positive structures and coordinated neurite extension, whereas Mus explants more commonly displayed a dispersed, sheet-like morphology with reduced neurite alignment. Importantly, neurite growth in Mus was not absent, but was spatially restricted and largely retained in the central, more three-dimensional region of the explant. Temporal analysis showed that the organized phenotype emerged progressively in Acomys but was not observed in Mus. While the organized phenotype was associated with increased neurite length, this effect was specific to the phenotype and did not fully account for the architectural divergence between species. Together, these findings indicate that a key species difference lies in the organization of neurite outgrowth and associated non-neuronal structure rather than in neurite extension alone. This study identifies explant architecture as a relevant readout of species-specific regenerative biology and suggests that non-neuronal microenvironmental organization may contribute to regeneration-permissive growth states.

Myofibroblasts are considered to be the villains of regeneration, causing scarring and fibrosis after damage in many systems of the body, including the skin. They are induced by the action of pro-fibrotic cytokines released from various immune cells and express α-smooth muscle actin (α-SMA). Acomys, the spiny mouse, does not fibrose after full-thickness skin injury, it instead will regenerate all the tissues removed. We compared the appearance and behavior of myofibroblasts after skin injury in Mus (scarring) and Acomys (regenerating). In Mus, myofibroblasts appear soon after wounding, remain in the wound bed for 2 weeks, and then disappear. In contrast, Acomys myofibroblasts initially appear at the same time and location as Mus, but they disappear from the wound bed earlier. Strikingly, Acomys myofibroblasts, intensely expressing α-SMA, form a bridge between the two ends of the panniculus muscle, which remains for many weeks as the muscle regenerates completely. We suggest that this myofibroblast scaffold may be responsible for the regeneration of the panniculus carnosus, which occurs following full-thickness skin injuries in Acomys.

Stroke is a major cause of disability for adults over 40 years of age. While research into animal models has prioritized treatments aimed at diminishing post-stroke damage, no studies have investigated the response to a severe stroke injury in a highly regenerative adult mammal. Here we investigate the effects of transient ischemia on adult spiny mice, Acomys cahirinus, due to their ability to regenerate multiple tissues without scarring. Transient middle cerebral artery occlusion was performed and Acomys showed rapid behavioral recovery post-stroke yet failed to regenerate impacted brain regions. An Acomys brain atlas in combination with functional (f)MRI demonstrated recovery coincides with neuroplasticity. The strength and quality of the global connectome are preserved post-injury with distinct contralateral and ipsilateral brain regions compensating for lost tissue. Thus, we propose Acomys recovers functionally from an ischemic stroke injury not by tissue regeneration but by altering its brain connectome.

The African spiny mouse (Acomys cahirinus) is a unique mammalian model of tissue regeneration, regenerating 4 mm ear-hole punches with cartilage, adipocytes, hair follicles, and muscle. However, the time to regenerate ear tissue varies from 20 to 90 days and muscle regeneration is inconsistent. Some report that ≥3-years and 9-week-old older spiny mice have delayed regeneration compared to 2-month and 3-week-old mice, respectively, without investigation on the regenerative capacity of muscle. We thought that delayed regeneration and inconsistent muscle regeneration could be linked via age-related nerve degeneration. While the current study found that spiny mice aged 6–9 months had delayed regeneration compared to 3–4 month-old spiny mice, the capacity of muscle regeneration was unrelated to age, and there was little evidence for age-related nerve degeneration. Instead, the regeneration of muscle, cartilage and adipocytes was spatially heterogeneous, regardless of age, declining in amount from the proximal to distal region of the regenerated tissue. Also, cartilage regeneration in the distal region was decreased in ≥22-month-old Acomys and adipocyte regeneration was decreased in those older than 6 months, compared to 3–4 month olds. While the underlying mechanisms for delayed and spatially heterogenous regeneration remain unclear, age and the spatial region of the regenerated tissue should be considered in experimental designs with spiny mice.

Neurodegenerative proteinopathies such as Alzheimer’s Disease are characterized by abnormal protein aggregation and neurodegeneration. Neuroresilience or regenerative strategies to prevent neurodegeneration, preserve function, or restore lost neurons may have the potential to combat human proteinopathies; however, the adult human brain possesses a limited capacity to replace lost neurons. In contrast, axolotls (Ambystoma mexicanum) show robust brain regeneration. To determine whether axolotls may help identify potential neuroresilience or regenerative strategies in humans, we first interrogated whether axolotls express putative proteins homologous to human proteins associated with neurodegenerative diseases. We compared the homology between human and axolotl proteins implicated in human proteinopathies and found that axolotls encode proteins highly similar to human microtubule-binding protein tau (tau), amyloid precursor protein (APP), and β-secretase 1 (BACE1), which are critically involved in human proteinopathies like Alzheimer’s Disease. We then tested monoclonal Tau and BACE1 antibodies previously used in human and rodent neurodegenerative disease studies using immunohistochemistry and western blotting to validate the homology for these proteins. These studies suggest that axolotls may prove useful in studying the role of these proteins in disease within the context of neuroresilience and repair.

Bite wounds due to aggression in male laboratory mice (Mus musculus) are a major welfare concern, often leading to attrition, chronic activation of the innate immune system, and significant impacts on the experimental results derived from the use of these animals as models. Bite wounding within the home-cage of spiny mice (Acomys cahirinus)—a valuable research model for wound healing and menstruation—is poorly characterized. While we have anecdotally observed frequent bite wounding in Acomys, the frequency of aggression within the home-cage, the severity of the bite wounds, and the types of dominance structures remain unstudied. Here, we report that 46% of Acomys cages in our colony had at least one bite wound over the course of a year and that same-sex pairs fought in the home-cage 10% of the time during their dark/active phase. Both sexes inflicted wounds and frequently engaged in agonistic behaviors, even with stable dominance structures. We found that females inflicted less severe bite wounds in same-sex housing. Also, aged females in same-sex pairs were never observed fighting, and no bite wounds were observed in aged Acomys. These results suggest that we should consider whether bite wounding negatively impacts our experimental results since physical trauma is known to alter menstrual cycling and healing.