A mouse model for monitoring islet cell genesis and developing therapies for diabetes

Autor: Yoshinori Shimajiri, Michael S. German, Shuhong Zhao, Nina Kishimoto, David W. Scheel, Juehu Wang, Yasuhiro Kosaka, Francis C. Lynn
Rok vydání: 2010
Předmět:
Organogenesis
Cell
Medicine (miscellaneous)
lcsh:Medicine
Mice
0302 clinical medicine
Immunology and Microbiology (miscellaneous)
Basic Helix-Loop-Helix Transcription Factors
Transgenes
0303 health sciences
geography.geographical_feature_category
Receptors
Notch
Cell sorting
Islet
3. Good health
Cell biology
Growth Differentiation Factors
medicine.anatomical_structure
Bone Morphogenetic Proteins
Models
Animal
Alkaline phosphatase
lcsh:RB1-214
Signal Transduction
Genetically modified mouse
medicine.medical_specialty
endocrine system
Green Fluorescent Proteins
Neuroscience (miscellaneous)
Notch signaling pathway
Mice
Transgenic
Nerve Tissue Proteins
Biology
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Islets of Langerhans
Fetus
Internal medicine
medicine
lcsh:Pathology
Diabetes Mellitus
Animals
Humans
Cell Lineage
Resource Article
Progenitor cell
030304 developmental biology
geography
lcsh:R
Alkaline Phosphatase
Embryonic stem cell
Endocrinology
030217 neurology & neurosurgery
Zdroj: Disease Models & Mechanisms
Disease Models & Mechanisms, Vol 4, Iss 2, Pp 268-276 (2011)
ISSN: 1754-8411
Popis: 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.
Databáze: OpenAIRE
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