The spiny mouse (Acomys species) has emerged as an exciting research organism due to its remarkable ability to undergo scarless regeneration of skin wounds and ear punches. Excitingly, Acomys species demonstrate scar-free healing in a wide-range of tissues beyond the skin. In this perspective article, we discuss published findings from a variety of tissues to highlight how this emerging research organism could shed light on numerous clinically relevant human diseases. We also discuss the challenges of working with this emerging research organism and suggest strategies for future Acomys-inspired research.

The manner in which laboratory rodents are housed is driven by economics (minimal use of space and resources), ergonomics (ease of handling and visibility of animals), hygiene, and standardization (reduction of variation). This has resulted in housing conditions that lack sensory and motor stimulation and restrict the expression of species-typical behavior. In mice, such housing conditions have been associated with indicators of impaired welfare, including abnormal repetitive behavior (stereotypies, compulsive behavior), enhanced anxiety and stress reactivity, and thermal stress. However, due to concerns that more complex environmental conditions might increase variation in experimental results, there has been considerable resistance to the implementation of environmental enrichment beyond the provision of nesting material. Here, using 96 C57BL/6 and SWISS female mice, respectively, we systematically varied environmental enrichment across four levels spanning the range of common enrichment strategies: (1) bedding alone; (2) bedding + nesting material; (3) deeper bedding + nesting material + shelter + increased vertical space; and (4) semi-naturalistic conditions, including weekly changes of enrichment items. We studied how these different forms of environmental enrichment affected measures of animal welfare, including home-cage behavior (time–budget and stereotypic behavior), anxiety (open field behavior, elevated plus-maze behavior), growth (food and water intake, body mass), stress physiology (glucocorticoid metabolites in fecal boluses and adrenal mass), brain function (recurrent perseveration in a two-choice guessing task) and emotional valence (judgment bias). Our results highlight the difficulty in making general recommendations across common strains of mice and for selecting enrichment strategies within specific strains. Overall, the greatest benefit was observed in animals housed with the greatest degree of enrichment. Thus, in the super-enriched housing condition, stereotypic behavior, behavioral measures of anxiety, growth and stress physiology varied in a manner consistent with improved animal welfare compared to the other housing conditions with less enrichment. Similar to other studies, we found no evidence, in the measures assessed here, that environmental enrichment increased variation in experimental results.

A tacit assumption in laboratory animal research is that animals housed within the same cage or pen are phenotypically more similar than animals from different cages or pens, due to their shared housing environment. This assumption drives experimental design, randomization schemes, and statistical analysis plans, while neglecting social context. Here, we examined whether a domain of social context—social dominance—accounted for more phenotypic variation in mice than cage-identity. First, we determined that cages of mice could be categorized into one of three dominance hierarchies with varying degrees of dominance behavior between cage-mates, and low levels of agonistic behavior in the home-cage. Most groups formed dynamic hierarchies with unclear ranks, contrasting with recent accounts of stable transitive hierarchies in groups of mice. Next, we measured some phenotypic traits, and found that social dominance (i.e. dominance hierarchy type and degree of dominance behavior) consistently accounted for some phenotypic variation in all outcome measures, while cage-identity accounted for phenotypic variation in some measures but virtually no variation in others. These findings highlight the importance of considering biologically relevant factors, such as social dominance, in experimental designs and statistical plans.

The spiny mouse, Acomys spp., is a recently described model organism for regeneration studies. For a mammal, it displays surprising powers of regeneration because it does not fibrose (i.e. scar) in response to tissue injury as most other mammals, including humans, do. In this Primer article, we review these regenerative abilities, highlighting the phylogenetic position of the spiny mouse relative to other rodents. We also briefly describe the Acomys tissues that have been used for regeneration studies and the common features of their regeneration compared with the typical mammalian response. Finally, we discuss the contribution that Acomys has made in understanding the general principles of regeneration and elaborate hypotheses as to why this mammal is successful at regenerating.

The laboratory mouse is the most prevalent animal used in experimental procedures in the biomedical and behavioural sciences. Yet, many scientists fail to consider the animals’ social context. Within a cage, mice may differ in their behaviour and physiology depending on their dominance relationships. Therefore, dominance relationships may be a confounding factor in animal experiments. The current study housed male and female C57BL/6ByJ mice in same-sex groups of 5 in standard laboratory conditions and investigated whether dominance hierarchies were present and stable across three weeks, and whether mice of different dominance ranks varied consistently in behaviour and physiology. We found that dominance ranks of most mice changed with time, but were most stable between the 2^nd and 3^rd week of testing. Phenotypic measures were also highly variable, and we found no relation between dominance rank and phenotype. Further, we found limited evidence that variation in measures of phenotype was associated with cage assignment for either males or females. Taken together, these findings do not lend support to the general assumption that individual variation among mice is larger between cages than within cages.

Poor reproducibility is considered a serious problem in laboratory animal research, with important scientific, economic, and ethical implications. One possible source of conflicting findings in laboratory animal research are environmental differences between animal facilities combined with rigorous environmental standardization within studies. Due to phenotypic plasticity, study-specific differences in environmental conditions during development can induce differences in the animals’ responsiveness to experimental treatments, thereby contributing to poor reproducibility of experimental results. Here, we studied how variation in weaning age (14–30 days) and housing conditions (single versus group housing) affects the phenotype of SWISS mice as measured by a range of behavioral and physiological outcome variables. Weaning age, housing conditions, and their interaction had little effect on the development of stereotypies, as well as on body weight, glucocorticoid metabolite concentrations, and behavior in the elevated plus-maze and open field test. These results are surprising and partly in conflict with previously published findings, especially with respect to the effects of early weaning. Our results thus question the external validity of previous findings and call for further research to identify the sources of variation between replicate studies and study designs that produce robust and reproducible experimental results.