Expression of human cell cycle regulators in the primary cell line of the African savannah elephant (loxodonta africana) increases proliferation until senescence, but does not induce immortalization

The African savannah elephant (Loxodonta africana) is one of the critically endangered animals. Conservation of genetic and cellular resources is important for the promotion of wild life-related research. Although primary cultured cells are a useful model for the physiology and genomics of the wild-type animals, their distribution is restricted due to the limited number of cell divisions allowed in them. Here, we tried to immortalize a primary cell line of L. africana with by overexpressing human mutant form of cyclin-dependent kinase 4 (CDK4R24C), cyclin D, and telomerase (TERT). It has been shown before that the combination of human CDK4R24C, cyclin D, and TERT induces the efficient cellular immortalization of cells derived from humans, bovine, swine, and monkeys. Interestingly, although the combination of these three genes extended the cellular proliferation of the L. africana-derived cells, they did not induce cellular immortalization. This study suggest that control of cellular senescence in L. africana-derived cells would be different molecular mechanisms compared to those governing human, bovine, swine, and monkey cells.