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How changes in brain scaling relate to altered behavior is an important question in neurodevelopmental disorder research. Mice with germline Pten haploinsufficiency (Pten+/-) closely mirror the abnormal brain scaling and behavioral deficits seen in humans with macrocephaly/autism syndrome, which is caused by PTEN mutations. We explored whether deviation from normal patterns of growth can predict behavioral abnormalities. Brain regions associated with sensory processing (e.g., pons and inferior colliculus) had the biggest deviations from expected volume. While Pten+/- mice showed little or no abnormal behavior on most assays, both sexes showed sensory deficits, including impaired sensorimotor gating and hyporeactivity to high-intensity stimuli. Developmental analysis of this phenotype showed sexual dimorphism for hyporeactivity. Mapping behavioral phenotypes of Pten+/- mice onto relevant brain regions suggested abnormal behavior is likely when associated with relatively enlarged brain regions, while unchanged or relatively decreased brain regions have little predictive value.

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