TALEN-Mediated Gene Mutagenesis in Rhesus and Cynomolgus Monkeys
2014-02-13
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.
Abstract:
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.
