Altered Primary Somatosensory Neuron Development in a Pten Heterozygous Model for Autism Spectrum Disorder.

Scientists studied mice with a genetic change linked to autism to understand sensory sensitivities. They found that these mice had unusual responses to touch and other sensations. The problem started early in development when special nerve cells that carry sensory information weren't developing normally. This research helps explain why many autistic people experience sensory differences like being over- or under-sensitive to touch, sound, or other sensations.

This study investigated sensory abnormalities in autism using Pten heterozygous mice, a genetic model for syndromic autism spectrum disorder. Researchers found that mice with Pten mutations showed altered responses to sensory stimuli and changes in dorsal root ganglia (DRG) neurons that transmit touch and other sensory information from the body to the brain. Through transcriptomic analysis, they identified disrupted development of specific DRG neuron subtypes, with changes emerging during early development due to dysregulated PTEN signaling pathways. The study also confirmed similar alterations in mice with a different ASD-associated Pten mutation, suggesting these findings may be conserved across different genetic models of autism.

Findings provide mechanistic insight into sensory processing differences in autism, particularly those with PTEN mutations. May inform future therapeutic approaches targeting sensory symptoms, though translation to clinical interventions requires further human studies.

Study conducted in mouse model which may not fully translate to human autism. Sample size not reported. Findings specific to Pten-related autism may not apply to other forms of ASD.

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 cellular mechanisms underlying the emergence of abnormal sensory sensitivity in ASD are not fully understood. Recent studies in rodent models of ASD identified differences in dorsal root ganglia (DRG) neurons that convey somatosensory information to the central nervous system. However, it is unknown how ASD-associated alterations in DRG neurons emerge during development and if these phenotypes are conserved across ASD models.

We examined Pten (phosphatase and tensin homolog) heterozygous mice (Pten) as a model for syndromic ASD and identified altered responses to sensory stimuli. Transcriptomic and in vivo analysis identified alterations in subtype-specific markers of DRG neurons in Ptenmice, emerging during early DRG development and involving dysregulation of signaling pathways downstream of PTEN. Finally, we show that mice harboring an ASD-associated mutation (Pten) show nearly identical alterations in the expression of somatosensory neuron subtype-specific markers. These results show that precise levels of PTEN are required for proper somatosensory development and provide insight into the molecular and cellular basis of sensory abnormalities in a model for syndromic ASD.