PTEN Affects Brain Development

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Science  19 May 2006:
Vol. 312, Issue 5776, pp. 975
DOI: 10.1126/science.312.5776.975c

Mutations in the tumor suppressor PTEN (phosphatase and tensin homolog on chromosome ten) are associated not only with tumor development but also with several brain disorders. Intriguingly, PTEN mutations have been reported in individuals with autism spectrum disorders (ASD) occurring in conjunction with macrocephaly. Kwon et al. used mutant mice in which Pten was deleted in a subset of differentiated neurons in the hippocampus and cerebral cortex to investigate the effects of PTEN on brain development and behavior. The mutant mice exhibited behavior evocative of that of individuals with ASD: atypical social interactions, exaggerated responses to stressful sensory stimuli, and atypical responses in paradigms designed to assess anxiety and learning. Their brains were enlarged in the regions in which Pten was deleted; this was associated with hypertrophy of the cell bodies of Pten-negative neurons as well as increased and abnormal growth of neuronal processes. The hypertrophied neurons showed increased phosphorylation of downstream targets of Akt signaling. Thus, abnormal activation of Akt signaling in a subset of neurons appears to promote macrocephaly and behaviors that resemble some of those associated with ASD. — EMA

Neuron 50, 377 (2006).

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