Beyond the mouse: non-rodent animal models for study of early mammalian development and biomedical research

Abstract

The preimplantation development of mammals generally follows the same plan. It starts with the formation of a totipotent zygote, and through consecutive cleavage divisions and differentiation events leads to blastocyst formation. However, the intervening events may differ between species. The regulation of these processes has been extensively studied in the mouse, which displays some unique features among eutherian mammals. Farm animals such as pigs, cattle, sheep and rabbits share several similarities with one another, and with the human developmental plan. These include the timing of epigenetic reprogramming, the moment of embryonic genome activation and the developmental time-frame. Recently, efficient techniques for genetic modification have been established for large domestic animals. Genome sequences and gene manipulation tools are now available for cattle, pigs, sheep and goats, and a larger number of genetically engineered livestock is now accessible for biomedical research. Yet, these animals still make up less than 0.5% of animals in research, mainly due to our inadequate knowledge of the processes responsible for pluripotency maintenance (to date no stable naïve embryonic stem cell lines have been established) and early development. In this review, we highlight our present knowledge of the key preimplantation events in the 3 non-rodent species which present the highest potential for biomedical research related to early embryonic development: cattle, which offer an excellent model to study human in vitro embryo development, pigs which emerge as models to study the long-term effects of gene-based therapies and rabbits, which in many aspects of embryology resemble the human.

MiR-144-3p Enhances Cardiac Fibrosis After Myocardial Infarction by Targeting PTEN

“…Previous studies have suggested that pigs are a valuable biomedical model based the similarly genomic and physiological features to humans (Groenen et al, 2012; Madeja et al, 2019), and much evidence has indicated that pigs have been widely used as animal model in studies associated MI (Gabisonia et al, 2019; Lopez et al, 2019). In this study, the potential miRNAs that might involve in the processes of cardiac fibrosis after MI were identified in the miniature pigs.…”

Understanding and Treating Niemann–Pick Type C Disease: Models Matter

“…There are numerous reasons for the slow progress such as rare occurrence, molecular complexity, and variability of symptoms. However, a decisive factor is the availability, quality, and use of experimental models [4][5][6][7][8][9][10][11][12][13]. NPC is a prime example for a disease that lacks a curative therapy despite impressive breakthroughs within the last decades [14][15][16][17] and rapidly growing publication counts (Appendix A, Figure 1).…”

A New Toolbox in Experimental Embryology—Alternative Model Organisms for Studying Preimplantation Development

“…Where the mouse shows unique regulatory mechanisms, other animals share great similarities in their developmental plan. The moment of zygotic genome activation, the first lineage differentiations and maintenance of pluripotency are some aspects that are not always conserved between species, but are very similar in cows and pigs compared to humans (reviewed in [ 1 , 2 , 3 ]). Furthermore, the scarcity of human embryos and the ethical and logistical challenges increase the need to work with other models.…”