Loss of the imprinted, non-coding Snord116 gene cluster in the interval deleted in the Prader Willi syndrome results in murine neuronal and endocrine pancreatic developmental phenotypes.

摘要: Global neurodevelopmental delay is a prominent characteristic of individuals with Prader-Willi syndrome (PWS). The neuromolecular bases for these delays are unknown. We identified neuroanatomical changes in the brains mice deficient gene minimal critical deletion region PWS (Snord116p-/m+). In Snord116p-/m+ mice, reduced primary forebrain neuron cell body size apparent embryonic day 15.5 fetuses, and persists until postnatal 30 cerebellar Purkinje neurons. Snord116 snoRNA cluster unknown function that can localize to nucleolus. neurons from reduction neuronal was associated decreased nucleolar size. also developmental endocrine pancreas animals persist into adulthood. Mice lacking have smaller pancreatic islets; within islet percentage δ-cells increased, while α-cells reduced. α-cell markers, Sst Hhex, upregulated isolated islets Ins1, Ins2, Pdx1, Nkx6-1, Pax6 downregulated. There 3-fold increase polyhormonal cells neonatal pancreata due primarily an co-positive somatostatin. may play role lineage specification. important processes brain as well pancreas.