Figure 3.

Snord116^p−/m+ mice display developmental changes in the endocrine pancreas that persist into adulthood. (A) There is no difference in the body weight of P0.5 Snord116^p−/m+ neonates compared with WT littermates. (B) There is a 23% decrease in the mean islet size (number of nuclei per islet) of P0.5 Snord116^p−/m+ mice compared with WT littermates. (C) The proportion of insulin-positive cells in the islet is unchanged; while the absolute number trends towards a 14% reduction, this does not reach statistical significance (Supplementary Material, Fig. S6). (D) There is a 3-fold increase in the proportion of somatostatin (SST) positive cells in the islet in Snord116^p−/m+ mice. (E) The percentage of glucagon (GCG) positive cells is decreased in islets of Snord116^p−/m+animals. (F) There is no difference in the percentage of pancreatic polypeptide (PP) positive cells. (G) Representative images of the hematoxylin and eosin (H&E) stain sections from which the number of nuclei per islet was quantified in P0.5 mice. (H,I) Representative images of insulin, glucagon, somatostin, and pancreatic polypeptide immunofluorescent staining. (J) Adult Snord116^p−/m+ mice are generally smaller than WT littermates. However, to minimize somatic size-related artifacts in comparisons of islet endocrine cell type populations, body weight-matched adult wild type and Snord116^p−/m+ mice were selected. (K) The mean islet size is decreased by 32%. In adult Snord116^p−/m+ mice compared with WT. (L) In adult Snord116^p−/m+the proportion of insulin positive cells in the islet is unchanged in adult mice. (M) The percentage of somatostatin positive cells are increased 1.5 fold. (N) The percentage of glucagon positive cells is decreased by 30% in Snord116^p−/m+ mice. (O) The proportion of pancreatic polypeptide positive cells is not altered in adult Snord116^p−/m+ mice. (P) Representative H&E images used for quantification of mean islet size. (Q–S) Representative images of the immunofluoresent staining for insulin, somatostatin, glucagon, and pancreatic polypeptide. (T,U) Ins1 and Ins2 gene expression levels are decreased in isolated islets from Snord116^p−/m+ adult mice compared with WT. (V) Sst gene expression levels are 2-fold increased in Snord116^p−/m+ isolated islets. (W–Y) There is no difference in the gene expression levels of Gcg, Ppy, or Ghrl in adult isolated islets.