Altered primary somatosensory neuron development in a heterozygous model for autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social interactions, repetitive behaviors, and hyper- or hyposensitivity to sensory stimuli. The mechanisms underlying the emergence of sensory features in ASD are not fully understood, but recent studies in rodent models highlight that these may result from differences in primary sensory neurons themselves. We examined sensory behaviors in a haploinsufficient mouse model ( ) for syndromic ASD and identified elevated responses to mechanical stimuli and a higher threshold to thermal responses.

Germline nuclear-predominant Pten murine model exhibits impaired social and perseverative behavior, microglial activation, and increased oxytocinergic activity.

Background: Autism spectrum disorder (ASD) has a strong genetic etiology. Germline mutation in the tumor suppressor gene PTEN is one of the best described monogenic risk cases for ASD. Animal modeling of cell-specific Pten loss or mutation has provided insight into how disruptions to the function of PTEN affect neurodevelopment, neurobiology, and social behavior.

Decreased nuclear Pten in neural stem cells contributes to deficits in neuronal maturation.

Background: PTEN, a syndromic autism spectrum disorder (ASD) risk gene, is mutated in approximately 10% of macrocephalic ASD cases. Despite the described genetic association between PTEN and ASD and ensuing studies, we continue to have a limited understanding of how PTEN disruption drives ASD pathogenesis and maintenance.

Methods: We derived neural stem cells (NSCs) from the dentate gyrus (DG) of Pten mice, a model that recapitulates PTEN-ASD phenotypes.