Journal article
Enhanced Nociception in Angelman Syndrome Model Mice
The Journal of neuroscience, Vol.37(42), pp.10230-10239
10/18/2017
DOI: 10.1523/JNEUROSCI.1018-17.2017
PMCID: PMC5647775
PMID: 28931574
Abstract
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.
Details
- Title: Subtitle
- Enhanced Nociception in Angelman Syndrome Model Mice
- Creators
- Eric S McCoy - Department of Cell Biology and Physiology and University of North Carolina Neuroscience CenterBonnie Taylor-Blake - Department of Cell Biology and Physiology and University of North Carolina Neuroscience CenterMegumi Aita - Department of Cell Biology and Physiology and University of North Carolina Neuroscience CenterJeremy M Simon - Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599Benjamin D Philpot - Carolina Institute for Developmental Disabilities, andMark J Zylka - Carolina Institute for Developmental Disabilities, and
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.37(42), pp.10230-10239
- Publisher
- United States
- DOI
- 10.1523/JNEUROSCI.1018-17.2017
- PMID
- 28931574
- PMCID
- PMC5647775
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Grant note
- R01 NS081127 / NINDS NIH HHS P30 NS045892 / NINDS NIH HHS P30 ES010126 / NIEHS NIH HHS U54 HD079124 / NICHD NIH HHS DP1 ES024088 / NIEHS NIH HHS R01 NS085093 / NINDS NIH HHS
- Language
- English
- Date published
- 10/18/2017
- Academic Unit
- Periodontics
- Record Identifier
- 9984065815202771
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