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The role of cells of the diffuse neuroendocrine system in development and maintenance of individual organs and tissues remains poorly understood. Here we identify a regulatory region sufficient for accurate  in vivo  expression of synaptophysin (SYP), a common marker of neuroendocrine differentiation, and report generation of Tg( Syp-EGFP loxP -DTA)147 Ayn   ( SypELDTA ) mice suitable for flexible organ-specific ablation of neuroendocrine cells. These mice express EGFP and diphtheria toxin fragment A (DTA) in SYP positive cells before and after Cre- loxP  mediated recombination, respectively. As a proof of principle, we have crossed  SypELDTA  mice with  EIIA-Cre  and  PB-Cre4  mice.  EIIA-Cre  mice express Cre recombinase in a broad range of tissues, while  PB-Cre4  mice specifically express Cre recombinase in the prostate epithelium. Double transgenic  EIIA-Cre; SypELDTA  embryos exhibited massive cell death in SYP positive cells. At the same time,  PB-Cre4; SypELDTA  mice showed a substantial decrease in the number of neuroendocrine cells and associated prostate hypotrophy. As no increase in cell death and/or Cre- loxP  mediated recombination was observed in non-neuroendocrine epithelium cells, these results suggest that neuroendocrine cells play an important role in prostate development. High cell type specificity of  Syp  locus-based cassette and versatility of generated mouse model should assure applicability of these resources to studies of neuroendocrine cell functions in various tissues and organs.

Detection and Organ-Specific Ablation of Neuroendocrine Cells by Synaptophysin Locus-Based BAC Cassette in Transgenic Mice