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Unexpected effects of the MIP‐Cre(ER) transgene and tamoxifen on β‐cell growth in C57Bl6/J male mice

Transgenic mouse models have been fundamental in the discovery of factors that regulate β‐cell development, mass, and function. Several groups have recently shown that some of these models display previously uncharacterized phenotypes due to the transgenic system itself. These include impaired islet...

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Autores principales: Carboneau, Bethany A., Le, Thao D. V., Dunn, Jennifer C., Gannon, Maureen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037909/
https://www.ncbi.nlm.nih.gov/pubmed/27670405
http://dx.doi.org/10.14814/phy2.12863
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author Carboneau, Bethany A.
Le, Thao D. V.
Dunn, Jennifer C.
Gannon, Maureen
author_facet Carboneau, Bethany A.
Le, Thao D. V.
Dunn, Jennifer C.
Gannon, Maureen
author_sort Carboneau, Bethany A.
collection PubMed
description Transgenic mouse models have been fundamental in the discovery of factors that regulate β‐cell development, mass, and function. Several groups have recently shown that some of these models display previously uncharacterized phenotypes due to the transgenic system itself. These include impaired islet function and increased β‐cell mass due to the presence of a human growth hormone (hGH) minigene as well as impaired β‐cell proliferation in response to tamoxifen (TM) administration. We aimed to determine how these systems impact β‐cell mass and proliferation during high fat diet (HFD). To this end, we utilized C57Bl6/J male MIP‐Cre(ER) mice, which are known to express hGH, or wild‐type (WT) mice treated with vehicle corn oil or TM. In the absence of TM, MIP‐Cre(ER) mice fed a chow diet have increased β‐cell mass due to hypertrophy, whereas replication is unchanged. Similarly, after 1 week on HFD, MIP‐Cre(ER) mice have increased β‐cell mass compared to WT, and this is due to hypertrophy rather than increased proliferation. To assess the impact of TM on β‐cell proliferation and mass, WT mice were treated with vehicle corn oil or TM and then fed a chow diet or HFD for 3 days. We observed that TM‐treated mice have improved glucose homeostasis on chow diet but impaired β‐cell proliferation in response to 3 days HFD feeding. These results unveil additional complications associated with commonly used pancreas‐specific mouse models.
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spelling pubmed-50379092016-10-19 Unexpected effects of the MIP‐Cre(ER) transgene and tamoxifen on β‐cell growth in C57Bl6/J male mice Carboneau, Bethany A. Le, Thao D. V. Dunn, Jennifer C. Gannon, Maureen Physiol Rep Original Research Transgenic mouse models have been fundamental in the discovery of factors that regulate β‐cell development, mass, and function. Several groups have recently shown that some of these models display previously uncharacterized phenotypes due to the transgenic system itself. These include impaired islet function and increased β‐cell mass due to the presence of a human growth hormone (hGH) minigene as well as impaired β‐cell proliferation in response to tamoxifen (TM) administration. We aimed to determine how these systems impact β‐cell mass and proliferation during high fat diet (HFD). To this end, we utilized C57Bl6/J male MIP‐Cre(ER) mice, which are known to express hGH, or wild‐type (WT) mice treated with vehicle corn oil or TM. In the absence of TM, MIP‐Cre(ER) mice fed a chow diet have increased β‐cell mass due to hypertrophy, whereas replication is unchanged. Similarly, after 1 week on HFD, MIP‐Cre(ER) mice have increased β‐cell mass compared to WT, and this is due to hypertrophy rather than increased proliferation. To assess the impact of TM on β‐cell proliferation and mass, WT mice were treated with vehicle corn oil or TM and then fed a chow diet or HFD for 3 days. We observed that TM‐treated mice have improved glucose homeostasis on chow diet but impaired β‐cell proliferation in response to 3 days HFD feeding. These results unveil additional complications associated with commonly used pancreas‐specific mouse models. John Wiley and Sons Inc. 2016-09-26 /pmc/articles/PMC5037909/ /pubmed/27670405 http://dx.doi.org/10.14814/phy2.12863 Text en © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Carboneau, Bethany A.
Le, Thao D. V.
Dunn, Jennifer C.
Gannon, Maureen
Unexpected effects of the MIP‐Cre(ER) transgene and tamoxifen on β‐cell growth in C57Bl6/J male mice
title Unexpected effects of the MIP‐Cre(ER) transgene and tamoxifen on β‐cell growth in C57Bl6/J male mice
title_full Unexpected effects of the MIP‐Cre(ER) transgene and tamoxifen on β‐cell growth in C57Bl6/J male mice
title_fullStr Unexpected effects of the MIP‐Cre(ER) transgene and tamoxifen on β‐cell growth in C57Bl6/J male mice
title_full_unstemmed Unexpected effects of the MIP‐Cre(ER) transgene and tamoxifen on β‐cell growth in C57Bl6/J male mice
title_short Unexpected effects of the MIP‐Cre(ER) transgene and tamoxifen on β‐cell growth in C57Bl6/J male mice
title_sort unexpected effects of the mip‐cre(er) transgene and tamoxifen on β‐cell growth in c57bl6/j male mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037909/
https://www.ncbi.nlm.nih.gov/pubmed/27670405
http://dx.doi.org/10.14814/phy2.12863
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