A concise review of common animal models for the study of limb regeneration

Figures & data

FIGURE 1. Regenerative capacity between urodeles and mammals during development. Urodeles (e.g., axolotl and newt) are the only known vertebrates that can perfectly regenerate different body parts throughout their life while mammals (e.g., mice and rats) are very limited in terms of epimorphic regeneration. It is known that the full regeneration of mammals limb is only limited to digit tips. During the first trimester of gestation, mammals are able to perfectly regenerate their digit tips, but this capacity seems to drop with aging.¹² The figure is modified from Roy S et al.¹² pRb: RetinSSSoblastoma protein; TGF-β: Transforming growth factor-β.

TABLE 1. Comparisons of advantages and disadvantages among various animal models of limb regeneration.

Model	Injury	Advantages	Disadvantages	References
Cockroach	whole limb amputation	identification of similarities across kingdoms, extremely cheap, minimal regulation	not ideal model for human response or mimic human disease situation	^8
Zebrafish	whole limb (fin) amputation	well documented genome, vertebrae animal model, sleep cycle, fast growth, high degree of regeneration, less regulation	not ideal model for human response or mimic human disease situation	^52,^57,58
Axolotl	whole limb amputation	extensive regeneration (principle in study of regeneration), good for identifying mechanisms, less regulation	not ideal model for human response or mimic human disease situation	^11,15-17,19,^59,60
Mouse	ischemia, digit amputation, muscle dystrophy	well documented genome, many variants and transgenic strains, mammalian, fast maturation rate, relative cheap model	findings may not be transferrable to human clinical trials.	^21,34,^61-64
Rat	innervation, digit amputation, ischemia	well documented genome, many variants and transgenic strains, mammalian, fast maturation rate, larger than mice, relative cheap model	similar to mice, but more expensive to maintain than mice, findings may not be transferrable to human	^41,^66-70
Dog	bone or ligament injury	large, highly active, cheaper than horse, useful for larger mammal study, especially as pre-clinical trial, the findings may be transferrable to human	longer mature period than rodents, higher quality of care demanded, special facilities required, expensive, ethic concern	^46,49,^71
Horse	ligament injury	large mammal, highly active (wear-prone), findings may be transferrable to human	more expensive, long maturation time, extension demanding facilities necessary, ethic concern	^47,48

Roy S, Gatien S. Regeneration in axolotls: a model to aim for! Exp Gerontol 2008; 43:968-73; PMID:18814845; http://dx.doi.org/10.1016/j.exger.2008.09.003

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French V. Leg regeneration in the cockroach, Blatella germanica. II. Regeneration from a non-congruent tibial graft/host junction. J Embryol Exp Morphol 1976; 35:267-301; PMID:939940

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Olsen AS, Sarras MP, Jr, Intine RV. Limb regeneration is impaired in an adult zebrafish model of diabetes mellitus. Wound Repair Regen 2010; 18:532-42; PMID:20840523; http://dx.doi.org/10.1111/j.1524-475X.2010.00613.x

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Cheng L, Liu Y, Zhao H, Zhang W, Guo YJ, Nie L. Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats. Biochem Biophys Res Commun 2013; 440:330-5; PMID:24076387; http://dx.doi.org/10.1016/j.bbrc.2013.09.084

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