Animal models of neurodevelopmental disorders with behavioral phenotypes

Genetic mutations in animals advance our understanding of disease mechanisms and treatments of neurodevelopmental disorders. Research with mutant mouse models is being extended to nonhuman primates whose brain development is closer to that of humans. This review summaries advances in mouse and nonhuman primate models.

Mutant mouse models recapitulate key symptoms in neurodevelopmental disorders. However, successful phenotypic reversal of symptoms in mouse models has not been replicated in human studies; this failure may be because of differences in the structure and physiology of the brain between rodents and humans. Rett syndrome MECP2 models and Phelan-McDermid syndrome where reduced expression of SH3 and multiple ankyrin repeat domains 3 (SHANK3) models have been introduced in nonhuman primates and are underway in other neurodevelopmental disorders.

Mutant mouse models in neurogenetic disorders continued to be pursued along with gene-edited and cell-based models in nonhuman primates. Established ethical guidelines are being followed and infrastructure being established to facilitate dissemination of primate transgenic models as they become available.