title: Detection and organ-specific ablation of neuroendocrine cells by synaptophysin locus-based BAC cassette in transgenic mice.
abstract: 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.
authors: Department of Biomedical Sciences, Cornell University, Ithaca, New York, United States of America.
authors: Chieh-Yang
authors: CY
authors: Cheng
authors: Zongxiang
authors: Z
authors: Zhou
authors: Alexander Yu
authors: AY
authors: Nikitin
mesh_terms: D000818:Animals; D001483:Base Sequence; D016923:Cell Death; D002460:Cell Line; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics*; D017124:Conserved Sequence; D004622:Embryo, Mammalian / Q000166:cytology; D015870:Gene Expression; D005818:Genetic Engineering; D056426:Genetic Loci; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D055099:Neuroendocrine Cells / Q000502:physiology*; D009928:Organ Specificity; D011467:Prostate / Q000166:cytology; D037941:Silencer Elements, Transcriptional; D016708:Synaptophysin / Q000235:genetics*; D019076:Transgenes
chemical_list: D016708:Synaptophysin; C569015:Syp protein, mouse
references: Prog Histochem Cytochem. 2003;38(2):155-272
references: 12756892
references: Lab Invest. 1988 Jul;59(1):5-24
references: 2839735
references: Gene. 1991 Mar 15;99(2):197-204
references: 1902431
references: Am J Surg Pathol. 1998 Oct;22(10):1267-76
references: 9777989
references: Cancer Res. 2006 Aug 15;66(16):7889-98
references: 16912162
references: Mech Dev. 2001 Mar;101(1-2):61-9
references: 11231059
references: Nature. 2008 Dec 11;456(7223):804-8
references: 18946470
references: Cancer Res. 2007 Jun 15;67(12):5683-90
references: 17553900
references: Biol Reprod. 1986 Jun;34(5):961-71
references: 3730488
references: J Biol Chem. 1989 Sep 15;264(26):15261-7
references: 2768263
references: Eur J Neurosci. 2005 Nov;22(9):2216-30
references: 16262660
references: Scand J Gastroenterol. 2003 May;38(5):451-5
references: 12795452
references: Science. 1989 Dec 1;246(4934):1165-8
references: 2531465
references: Gynecol Endocrinol. 2012 Mar;28 Suppl 1:27-32
references: 22394301
references: Cancer Res. 1988 Jul 15;48(14):4078-82
references: 3383200
references: Am J Pathol. 1987 Feb;126(2):243-57
references: 3103452
references: Lab Invest. 2006 May;86(5):425-44
references: 16568108
references: Diabetologia. 2000 Apr;43(4):393-410
references: 10819232
references: Am J Pathol. 1991 Apr;138(4):961-9
references: 2012179
references: Genes Dev. 1996 Aug 1;10(15):1870-9
references: 8756345
references: Lab Invest. 1985 Mar;52(3):239-42
references: 3974198
references: Curr Protoc Neurosci. 2005 May;Chapter 5:Unit 5.20
references: 18428622
references: Acta Physiol (Oxf). 2008 Feb;192(2):287-301
references: 18005392
references: Neuroscience. 1986 Oct;19(2):605-27
references: 3490633
references: Genome Biol. 2003;4(12):R79
references: 14659016
references: Cell Mol Neurobiol. 2010 Nov;30(8):1467-75
references: 21088883
references: Am J Transl Res. 2009 Feb 05;1(2):148-62
references: 19956427
references: Cancer Res. 2007 Aug 1;67(15):7525-33
references: 17671224
references: Eur J Biochem. 2003 Jan;270(1):2-9
references: 12492469
references: Science. 1987 Nov 20;238(4830):1142-4
references: 3120313
references: Nature. 2005 Aug 4;436(7051):725-30
references: 16079851
references: Lab Invest. 1985 Mar;52(3):257-63
references: 3974199
references: Cell Cycle. 2011 Nov 1;10(21):3629-30
references: 22024916
references: Prostate. 2003 May 15;55(3):219-37
references: 12692788
references: Arch Pathol Lab Med. 1989 Jul;113(7):790-6
references: 2787149
references: Proc Natl Acad Sci U S A. 1986 May;83(10):3500-4
references: 3010302
references: Nature. 1978 Dec 21-28;276(5690):834-6
references: 31568
references: J Cell Biol. 2005 Jul 4;170(1):81-90
references: 15983059
references: Auton Neurosci. 2005 Jun 15;120(1-2):10-7
references: 15927540
references: Prostate. 2007 Jun 15;67(9):968-75
references: 17440972
references: Am J Pathol. 1988 May;131(2):258-69
references: 3282444
references: Prostate. 1999 May;39(2):135-48
references: 10221570
references: N Engl J Med. 2004 Oct 7;351(15):1488-90
references: 15470210
references: Nat Genet. 1999 Jan;21(1):70-1
references: 9916792
references: J Cell Biol. 2002 Jun 24;157(7):1257-65
references: 12082083
references: Cancer Cell. 2003 Sep;4(3):209-21
references: 14522255
references: Curr Opin Oncol. 2008 Jan;20(1):1-12
references: 18043250
references: Cancer Res. 2001 Mar 1;61(5):2239-49
references: 11280793
references: J Neurochem. 1995 Jul;65(1):23-31
references: 7790865
references: Genesis. 2005 Nov;43(3):129-35
references: 16267821
references: Cancer Res. 1990 Sep 15;50(18):6068-74
references: 2168288
references: Hum Pathol. 1997 Dec;28(12):1373-8
references: 9416693
references: Arch Histol Cytol. 1995 Oct;58(4):379-96
references: 8562130
references: Respir Res. 2005 Oct 10;6:115
references: 16216130
references: Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5860-5
references: 8650183
references: J Mol Neurosci. 2012 Oct;48(2):429-40
references: 22528452