Zebrafish akt2 is essential for survival, growth, bone development, and glucose homeostasis.

As one of three akt isoforms, akt2 plays a key role in the regulation of widely divergent cellular processes in mammals. However, its role and underlying mechanisms in zebrafish remain largely unknown. To elucidate the function of akt2 in zebrafish, we generated zebrafish lacking akt2 gene via CRISPR/Cas9 technology. Akt2-null zebrafish exhibit partial lethality and severe growth deficiency, which is different from those observed in akt2-null mice. Furthermore, akt2-null zebrafish display deficiency in fin ray development, but their cartilage is not affected. Similar to observations in akt2-null mice, akt2-null zebrafish display impaired glucose homeostasis. However, in contrast to that in akt2-null mice, insulin level is lower in akt2-null zebrafish, implicating the symptoms of type I diabetes exhibited in akt2-null zebrafish. In addition, transcriptome analysis reveals that the genes involved in metabolism and osteogenesis are disturbed in akt2-null zebrafish. Taken together, these data not only support an important role of akt2 in zebrafish survival, growth, bone development and glucose homeostasis, but also suggest that akt2 has divergent functions between mice and zebrafish, even though they are evolutionarily conserved.