Enhanced Nociception in Angelman Syndrome Model Mice.

Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by mutation or deletion of the maternal allele. The maternal allele is expressed in nearly all neurons of the brain and spinal cord, whereas the paternal allele is repressed by an extremely long antisense transcript (). Little is known about expression of in the peripheral nervous system, where loss of maternal might contribute to AS phenotypes. Here we sought to examine maternal and paternal expression in DRGs neurons and to evaluate whether nociceptive responses were affected in AS model mice (global deletion of maternal allele; ). We found that most large-diameter proprioceptive and mechanosensitive DRG neurons expressed maternal and paternal In contrast, most small-diameter neurons expressed biallelically and had low to undetectable levels of Analysis of single-cell DRG transcriptomes further suggested that is expressed monoallelically in myelinated large-diameter neurons and biallelically in unmyelinated small-diameter neurons. Behavioral responses to some noxious thermal and mechanical stimuli were enhanced in male and female AS model mice; however, nociceptive responses were not altered by the conditional deletion of maternal in the DRG. These data suggest that the enhanced nociceptive responses in AS model mice are due to loss of maternal in the central, but not peripheral, nervous system. Our study provides new insights into sensory processing deficits associated with AS. Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss or mutation of the maternal allele. While sensory processing deficits are frequently associated with AS, it is currently unknown whether is expressed in peripheral sensory neurons or whether maternal deletion of affects somatosensory responses. Here, we found that is primarily expressed from the maternally inherited allele in myelinated large-diameter sensory neurons and biallelically expressed in unmyelinated small-diameter neurons. Nociceptive responses to select noxious thermal and mechanical stimuli were enhanced following global, but not sensory neuron-specific, deletion of maternal in mice. These data suggest that maternal loss of affects nociception via a central, but not peripheral mechanism, with implications for AS.