A mouse model for monitoring islet cell genesis and developing therapies for diabetes
SUMMARY Transient expression of the transcription factor neurogenin-3 marks progenitor cells in the pancreas as they differentiate into islet cells. We developed a transgenic mouse line in which the surrogate markers secreted alkaline phosphatase (SeAP) and enhanced green florescent protein (EGFP) c...
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The Company of Biologists
2011-03-01
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Series: | Disease Models & Mechanisms |
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doaj-1f904796f3c549ec97c222899ab17a352020-11-25T01:20:03ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112011-03-014226827610.1242/dmm.002998002998A mouse model for monitoring islet cell genesis and developing therapies for diabetesYoshinori ShimajiriYasuhiro KosakaDavid W. ScheelFrancis C. LynnNina KishimotoJuehu WangShuhong ZhaoMichael S. GermanSUMMARY Transient expression of the transcription factor neurogenin-3 marks progenitor cells in the pancreas as they differentiate into islet cells. We developed a transgenic mouse line in which the surrogate markers secreted alkaline phosphatase (SeAP) and enhanced green florescent protein (EGFP) can be used to monitor neurogenin-3 expression, and thus islet cell genesis. In transgenic embryos, cells expressing EGFP lined the pancreatic ducts. SeAP was readily detectable in embryos, in the media of cultured embryonic pancreases and in the serum of adult animals. Treatment with the γ-secretase inhibitor DAPT, which blocks Notch signaling, enhanced SeAP secretion rates and increased the number of EGFP-expressing cells as assayed by fluorescence-activated cell sorting (FACS) and immunohistochemistry in cultured pancreases from embryos at embryonic day 11.5, but not in pancreases harvested 1 day later. By contrast, treatment with growth differentiation factor 11 (GDF11) reduced SeAP secretion rates. In adult mice, partial pancreatectomy decreased, whereas duct ligation increased, circulating SeAP levels. This model will be useful for studying signals involved in islet cell genesis in vivo and developing therapies that induce this process.http://dmm.biologists.org/content/4/2/268 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yoshinori Shimajiri Yasuhiro Kosaka David W. Scheel Francis C. Lynn Nina Kishimoto Juehu Wang Shuhong Zhao Michael S. German |
spellingShingle |
Yoshinori Shimajiri Yasuhiro Kosaka David W. Scheel Francis C. Lynn Nina Kishimoto Juehu Wang Shuhong Zhao Michael S. German A mouse model for monitoring islet cell genesis and developing therapies for diabetes Disease Models & Mechanisms |
author_facet |
Yoshinori Shimajiri Yasuhiro Kosaka David W. Scheel Francis C. Lynn Nina Kishimoto Juehu Wang Shuhong Zhao Michael S. German |
author_sort |
Yoshinori Shimajiri |
title |
A mouse model for monitoring islet cell genesis and developing therapies for diabetes |
title_short |
A mouse model for monitoring islet cell genesis and developing therapies for diabetes |
title_full |
A mouse model for monitoring islet cell genesis and developing therapies for diabetes |
title_fullStr |
A mouse model for monitoring islet cell genesis and developing therapies for diabetes |
title_full_unstemmed |
A mouse model for monitoring islet cell genesis and developing therapies for diabetes |
title_sort |
mouse model for monitoring islet cell genesis and developing therapies for diabetes |
publisher |
The Company of Biologists |
series |
Disease Models & Mechanisms |
issn |
1754-8403 1754-8411 |
publishDate |
2011-03-01 |
description |
SUMMARY
Transient expression of the transcription factor neurogenin-3 marks progenitor cells in the pancreas as they differentiate into islet cells. We developed a transgenic mouse line in which the surrogate markers secreted alkaline phosphatase (SeAP) and enhanced green florescent protein (EGFP) can be used to monitor neurogenin-3 expression, and thus islet cell genesis. In transgenic embryos, cells expressing EGFP lined the pancreatic ducts. SeAP was readily detectable in embryos, in the media of cultured embryonic pancreases and in the serum of adult animals. Treatment with the γ-secretase inhibitor DAPT, which blocks Notch signaling, enhanced SeAP secretion rates and increased the number of EGFP-expressing cells as assayed by fluorescence-activated cell sorting (FACS) and immunohistochemistry in cultured pancreases from embryos at embryonic day 11.5, but not in pancreases harvested 1 day later. By contrast, treatment with growth differentiation factor 11 (GDF11) reduced SeAP secretion rates. In adult mice, partial pancreatectomy decreased, whereas duct ligation increased, circulating SeAP levels. This model will be useful for studying signals involved in islet cell genesis in vivo and developing therapies that induce this process. |
url |
http://dmm.biologists.org/content/4/2/268 |
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