Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA219170 | ENA |
REPOSITORIES: ENA
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Project description:ABSTRACT: The human growth hormone (hGH) minigene is frequently used in transgenic mouse lines to ensure proper transgene expression. Here, we show that hGH is expressed in islets isolated from the commonly used Pdx1-CreLate mouse model. Locally secreted hGH activates prolactin receptors on M-NM-2 cells causing phosphorylation of STAT5, and induces a pregnancy-like change in gene expression, augmented pancreatic M-NM-2 cell mass and insulin content. In addition, islets of Pdx1-CreLate mice had lower GLUT2 expression, reduced glucose-induced insulin release and were protected against the M-NM-2 cell toxin streptozotocin. As the hGH minigene is commonly used in a great number of Cre-driver and other transgenic mouse models in diabetes research, the currently reported profound phenotypic changes may necessitate the re-evaluation of a large amount of previously published work. Data obtained for the Pdx1-creLate and control samples were compaired to investigate the effect of hGH on the mRNA profile of islets. The data obtained from the islets of pregnant mice was added to the analysis to confirm the pregnacy-like phenotype in the Pdx1-creLate islets. The data of the different days of pregnancy was already described in Schraenen et al. 2010 (PMID: 20886204 and PMID: 20938637). Islets were isolated from Pdx1-creLate, control and pregnant mice for RNA extraction and hybridization on Affymetrix microarrays. For every condition, at least 3 biological replicates were used.
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Project description:ABSTRACT: The human growth hormone (hGH) minigene is frequently used in the derivation of transgenic mouse lines to enhance transgene expression. Although this minigene is present in the transgenes as a secondcistron, and thus not thought to be expressed, we found that three commonly used lines, Pdx1-CreLate, RIP-Cre, and MIP-GFP, each expressed significant amounts of hGH in pancreatic islets. Locally secreted hGH binds to prolactin receptors on β cells, activates STAT5 signaling, and induces pregnancy-like changes in gene expression, thereby augmenting pancreatic β cell mass and insulin content. In addition, islets of Pdx1-CreLate mice have lower GLUT2 expression and reduced glucose-induced insulin release and are protected against the β cell toxin streptozotocin. These findings may be important when interpreting results obtained when these and other hGH minigene-containing transgenic mice are used. Data obtained for the Pdx1-creLate and control samples were compaired to investigate the effect of hGH on the mRNA profile of islets. The data obtained from the islets of pregnant mice was added to the analysis to confirm the pregnacy-like phenotype in the Pdx1-creLate islets. The data of the different days of pregnancy was already described in Schraenen et al. 2010 (PMID: 20886204 and PMID: 20938637).
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