Persistent neuronal Ube3a expression in the suprachiasmatic nucleus of Angelman syndrome model mice.
Mutations or deletions of the maternal allele of the UBE3A gene cause Angelman syndrome (AS), a severe neurodevelopmental disorder. The paternal UBE3A/Ube3a allele becomes epigenetically silenced in most neurons during postnatal development in humans and mice; hence, loss of the maternal allele largely eliminates neuronal expression of UBE3A protein. However, recent studies suggest that paternal Ube3a may escape silencing in certain neuron populations, allowing for persistent expression of paternal UBE3A protein. Here we extend evidence in AS model mice (Ube3a(m-/p+)) of paternal UBE3A expression within the suprachiasmatic nucleus (SCN), the master circadian pacemaker. Paternal UBE3A-positive cells in the SCN show partial colocalization with the neuropeptide arginine vasopressin (AVP) and clock proteins (PER2 and BMAL1), supporting that paternal UBE3A expression in the SCN is often of neuronal origin. Paternal UBE3A also partially colocalizes with a marker of neural progenitors, SOX2, implying that relaxed or incomplete imprinting of paternal Ube3a reflects an overall immature molecular phenotype. Our findings highlight the complexity of Ube3a imprinting in the brain and illuminate a subpopulation of SCN neurons as a focal point for future studies aimed at understanding the mechanisms of Ube3a imprinting.
Department of Cell Biology &Physiology, UNC Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.|Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Kelly A
KA
Jones
Department of Cell Biology &Physiology, UNC Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Ji Eun
JE
Han
Department of Pharmacology &Toxicology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Jason P
JP
DeBruyne
Department of Cell Biology &Physiology, UNC Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.|Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Benjamin D
BD
Philpot
D000679:Amygdala / Q000378:metabolism; D017204:Angelman Syndrome / Q000235:genetics* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D018392:Genomic Imprinting; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000378:metabolism* / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
C502429:Ube3a protein, mouse; D044767:Ubiquitin-Protein Ligases