TALEN-Mediated Gene Mutagenesis in Rhesus and Cynomolgus Monkeys
Diagram of how MECP2 mutant monkey generated
As published in Cell Stem Cell on 13 February 2014, Liu et al. reported successful TALEN-mediated mutagenesis of an X-linked, Rett syndrome (RTT) gene, methyl-CpG binding protein 2 (MECP2), in both rhesus and cynomolgus monkeys. This is the first nonhuman primates model constructed by TALENs.
For details, refer to the paper:TALEN-Mediated Gene Mutagenesis in Rhesus and Cynomolgus Monkeys. Cell Stem Cell, 13 February 2014 doi: 10.1016/j.stem.2014.01.018.
Liu et al.
Recent advances in gene editing technology have introduced the potential for application of mutagenesis approaches in nonhuman primates to model human development and disease. Here we report successful TALEN-mediated mutagenesis of an X-linked, Rett syndrome (RTT) gene, methyl-CpG binding protein 2 (MECP2), in both rhesus and cynomolgus monkeys. Microinjection of MECP2-targeting TALEN plasmids into rhesus and cynomolgus zygotes leads to effective gene editing of MECP2 with no detected off-target mutagenesis. Male rhesus (2) and cynomolgous (1) fetuses carrying MECP2 mutations in various tissues including testes were miscarried during midgestation, consistent with RTT-linked male embryonic lethality in humans. One live delivery of a female cynomolgus monkey occurred after 162 days of gestation, with abundant MECP2 mutations in peripheral tissues. We conclude that TALEN-mediated mutagenesis can be an effective tool for genetic modeling of human disease in nonhuman primates.