Generation of animals allowing the conditional inactivation of the Pax4 gene

详细信息    查看全文

• 作者：Simon Kordowich (1)
  Palle Serup (2) (3)
  Patrick Collombat (4) (5)
  Ahmed Mansouri (1) (6)
  
• 关键词：Beta ; cells ; Pancreas ; Insulin ; Knockout ; Floxed allele ; Diabetes
• 刊名：Transgenic Research
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：21
• 期：6
• 页码：1215-1220
• 全文大小：948KB
• 参考文献：1. Brun T, Franklin I, St-Onge L, Biason-Lauber A, Schoenle EJ, Wollheim CB, Gauthier BR (2004) The diabetes-linked transcription factor PAX4 promotes {beta}-cell proliferation and survival in rat and human islets. J Cell Biol 167(6):1123鈥?135 CrossRef
  2. Collombat P, Mansouri A, Hecksher-Sorensen J, Serup P, Krull J, Gradwohl G, Gruss P (2003) Opposing actions of Arx and Pax4 in endocrine pancreas development. Genes Dev 17(20):2591鈥?603 CrossRef
  3. Collombat P, Hecksher-Sorensen J, Broccoli V, Krull J, Ponte I, Mundiger T, Smith J, Gruss P, Serup P, Mansouri A (2005) The simultaneous loss of Arx and Pax4 genes promotes a somatostatin-producing cell fate specification at the expense of the alpha- and beta-cell lineages in the mouse endocrine pancreas. Development 132(13):2969鈥?980. doi:10.1242/dev.01870 CrossRef
  4. Collombat P, Hecksher-Sorensen J, Serup P, Mansouri A (2006) Specifying pancreatic endocrine cell fates. Mech Dev 123(7):501鈥?12 CrossRef
  5. Collombat P, Xu X, Ravassard P, Sosa-Pineda B, Dussaud S, Billestrup N, Madsen OD, Serup P, Heimberg H, Mansouri A (2009) The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells. Cell 138(3):449鈥?62. doi:S0092-8674(09)00639-410.1016/j.cell.2009.05.035 CrossRef
  6. Copeland NG, Jenkins NA, Court DL (2001) Recombineering: a powerful new tool for mouse functional genomics. Nat Rev Genet 2(10):769鈥?79. doi:10.1038/3509355635093556 CrossRef
  7. Dymecki SM (1996) Flp recombinase promotes site-specific DNA recombination in embryonic stem cells and transgenic mice. Proc Natl Acad Sci U S A 93(12):6191鈥?196 CrossRef
  8. Hu He KH, Lorenzo PI, Brun T, Jimenez Moreno CM, Aeberhard D, Vallejo Ortega J, Cornu M, Thorel F, Gjinovci A, Thorens B, Herrera PL, Meda P, Wollheim CB, Gauthier BR (2011) In vivo conditional Pax4 overexpression in mature islet beta-cells prevents stress-induced hyperglycemia in mice. Diabetes 60(6):1705鈥?715. doi:10.2337/db10-1102 CrossRef
  9. Mansour SL, Thomas KR, Capecchi MR (1988) Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature 336(6197):348鈥?52. doi:10.1038/336348a0 CrossRef
  10. Mansouri A, Hallonet M, Gruss P (1996) Pax genes and their roles in cell differentiation and development. Curr Opin Cell Biol 8(6):851鈥?57 CrossRef
  11. Rath MF, Bailey MJ, Kim JS, Coon SL, Klein DC, Moller M (2009a) Developmental and daily expression of the Pax4 and Pax6 homeobox genes in the rat retina: localization of Pax4 in photoreceptor cells. J Neurochem 108(1):285鈥?94. doi:JNC576510.1111/j.1471-4159.2008.05765.x CrossRef
  12. Rath MF, Bailey MJ, Kim JS, Ho AK, Gaildrat P, Coon SL, Moller M, Klein DC (2009b) Developmental and diurnal dynamics of Pax4 expression in the mammalian pineal gland: nocturnal down-regulation is mediated by adrenergic-cyclic adenosine 3鈥?5鈥?monophosphate signaling. Endocrinology 150(2):803鈥?11. doi:10.1210/en.2008-0882 CrossRef
  13. Sosa-Pineda B (2004) The gene Pax4 is an essential regulator of pancreatic beta-cell development. Mol Cells 18(3):289鈥?94
  14. Sosa-Pineda B, Chowdhury K, Torres M, Oliver G, Gruss P (1997) The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas. Nature 386(6623):399鈥?02. doi:10.1038/386399a0 CrossRef
  15. Wang Q, Elghazi L, Martin S, Martins I, Srinivasan RS, Geng X, Sleeman M, Collombat P, Houghton J, Sosa-Pineda B (2008) Ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and duodenum. Dev Dyn 237(1):51鈥?1. doi:10.1002/dvdy.21379 CrossRef
  
• 作者单位：Simon Kordowich (1)
  Palle Serup (2) (3)
  Patrick Collombat (4) (5)
  Ahmed Mansouri (1) (6)
  
  1. Department of Molecular Cell Biology, Max-Planck Institute for Biophysical Chemistry, Am Fassberg, 37077, G枚ttingen, Germany
  2. Department of Developmental Biology, Hagedorn Research Institute, Niels Steensensvej 6, 2820, Gentofte, Denmark
  3. The Danish Stem Cell Center (DanStem), Copenhagen, Denmark
  4. Diabetes Genetics Team, Inserm, U1091, 06108, Nice, France
  5. Universit茅 de Nice Sophia-Antipolis, 06108, Nice, France
  6. Department of Clinical Neurophysiology, University of G枚ttingen, Robert-Koch Strasse 40, 37075, G枚ttingen, Germany
  
• ISSN：1573-9368

文摘

Pax4 belongs to the paired-box family of transcription factors. The analysis of loss- and gain-of-function mutant animals revealed that this factor plays a crucial role in the endocrine pancreas. Indeed, Pax4 is required for the genesis of insulin-producing beta-cells. Remarkably, the sole misexpression of Pax4 in glucagon-expressing cells is able to induce their regeneration, endow these with beta-cell features, and thereby counter chemically induced diabetes. However, the function of Pax4 in adult endocrine cells remains unclear. Herein, we report the generation of Pax4 conditional knockout mice that will allow the analysis of Pax4 function in mature beta-cells, as well as in the adult central nervous system.