Summary
Gene-editing technologies have made it feasible to create nonhuman
primate models for human genetic disorders. Here, we report detailed genotypes
and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys
serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which
is caused by loss-of-function mutations in the human MECP2
gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a
disease of females. Through a battery of behavioral analyses, including
primate-unique eye-tracking tests, in combination with brain imaging via MRI, we
found a series of physiological, behavioral, and structural abnormalities
resembling clinical manifestations of RTT. Moreover, blood transcriptome
profiling revealed that mutant monkeys resembled RTT patients in immune gene
dysregulation. Taken together, the stark similarity in phenotype and/or
endophenotype between monkeys and patients suggested that gene-edited RTT
founder monkeys would be of value for disease mechanistic studies as well as
development of potential therapeutic interventions for RTT.
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