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Phenotypic Characterization of MIP-CreERT1Lphi Mice With Transgene-Driven Islet Expression of Human Growth Hormone.

Publication ,  Journal Article
Oropeza, D; Jouvet, N; Budry, L; Campbell, JE; Bouyakdan, K; Lacombe, J; Perron, G; Bergeron, V; Neuman, JC; Brar, HK; Fenske, RJ; Meunier, C ...
Published in: Diabetes
November 2015

There is growing concern over confounding artifacts associated with β-cell-specific Cre-recombinase transgenic models, raising questions about their general usefulness in research. The inducible β-cell-specific transgenic (MIP-CreERT(1Lphi)) mouse was designed to circumvent many of these issues, and we investigated whether this tool effectively addressed concerns of ectopic expression and disruption of glucose metabolism. Recombinase activity was absent from the central nervous system using a reporter line and high-resolution microscopy. Despite increased pancreatic insulin content, MIP-CreERT mice on a chow diet exhibited normal ambient glycemia, glucose tolerance and insulin sensitivity, and appropriate insulin secretion in response to glucose in vivo and in vitro. However, MIP-CreERT mice on different genetic backgrounds were protected from high-fat/ streptozotocin (STZ)-induced hyperglycemia that was accompanied by increased insulin content and islet density. Ectopic human growth hormone (hGH) was highly expressed in MIP-CreERT islets independent of tamoxifen administration. Circulating insulin levels remained similar to wild-type controls, whereas STZ-associated increases in α-cell number and serum glucagon were significantly blunted in MIP-CreERT(1Lphi) mice, possibly due to paracrine effects of hGH-induced serotonin expression. These studies reveal important new insight into the strengths and limitations of the MIP-CreERT mouse line for β-cell research.

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Published In

Diabetes

DOI

EISSN

1939-327X

Publication Date

November 2015

Volume

64

Issue

11

Start / End Page

3798 / 3807

Location

United States

Related Subject Headings

  • Phenotype
  • Mice, Transgenic
  • Mice
  • Male
  • Insulin-Secreting Cells
  • Insulin
  • Hyperglycemia
  • Humans
  • Human Growth Hormone
  • Homeostasis
 

Citation

APA
Chicago
ICMJE
MLA
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Oropeza, D., Jouvet, N., Budry, L., Campbell, J. E., Bouyakdan, K., Lacombe, J., … Estall, J. L. (2015). Phenotypic Characterization of MIP-CreERT1Lphi Mice With Transgene-Driven Islet Expression of Human Growth Hormone. Diabetes, 64(11), 3798–3807. https://doi.org/10.2337/db15-0272
Oropeza, Daniel, Nathalie Jouvet, Lionel Budry, Jonathan E. Campbell, Khalil Bouyakdan, Julie Lacombe, Gabrielle Perron, et al. “Phenotypic Characterization of MIP-CreERT1Lphi Mice With Transgene-Driven Islet Expression of Human Growth Hormone.Diabetes 64, no. 11 (November 2015): 3798–3807. https://doi.org/10.2337/db15-0272.
Oropeza D, Jouvet N, Budry L, Campbell JE, Bouyakdan K, Lacombe J, et al. Phenotypic Characterization of MIP-CreERT1Lphi Mice With Transgene-Driven Islet Expression of Human Growth Hormone. Diabetes. 2015 Nov;64(11):3798–807.
Oropeza, Daniel, et al. “Phenotypic Characterization of MIP-CreERT1Lphi Mice With Transgene-Driven Islet Expression of Human Growth Hormone.Diabetes, vol. 64, no. 11, Nov. 2015, pp. 3798–807. Pubmed, doi:10.2337/db15-0272.
Oropeza D, Jouvet N, Budry L, Campbell JE, Bouyakdan K, Lacombe J, Perron G, Bergeron V, Neuman JC, Brar HK, Fenske RJ, Meunier C, Sczelecki S, Kimple ME, Drucker DJ, Screaton RA, Poitout V, Ferron M, Alquier T, Estall JL. Phenotypic Characterization of MIP-CreERT1Lphi Mice With Transgene-Driven Islet Expression of Human Growth Hormone. Diabetes. 2015 Nov;64(11):3798–3807.

Published In

Diabetes

DOI

EISSN

1939-327X

Publication Date

November 2015

Volume

64

Issue

11

Start / End Page

3798 / 3807

Location

United States

Related Subject Headings

  • Phenotype
  • Mice, Transgenic
  • Mice
  • Male
  • Insulin-Secreting Cells
  • Insulin
  • Hyperglycemia
  • Humans
  • Human Growth Hormone
  • Homeostasis