Impaired Islet Function in Commonly Used Transgenic Mouse Lines due to Human Growth Hormone Minigene Expression

被引：142

作者：

Brouwers, Bas ^{[1
]}

de Faudeur, Geoffroy ^{[2
]}

Osipovich, Anna B. ^{[3
,4
]}

Goyvaerts, Lotte ^{[2
]}

Lemaire, Katleen ^{[2
]}

Boesmans, Leen ^{[2
]}

Cauwelier, Elisa J. G. ^{[1
]}

Granvik, Mikaela ^{[2
]}

Pruniau, Vincent P. E. G. ^{[1
]}

Van Lommel, Leentje ^{[2
]}

Van Schoors, Jolien ^{[5
]}

Stancill, Jennifer S. ^{[3
,4
]}

Smolders, Ilse ^{[5
]}

Goffin, Vincent ^{[6
]}

Binart, Nadine ^{[7
]}

in't Veld, Peter ^{[8
]}

Declercq, Jeroen ^{[1
]}

Magnuson, Mark A. ^{[3
,4
]}

Creemers, John W. M. ^{[1
]}

Schuit, Frans ^{[2
]}

Schraenen, Anica ^{[2
]}

机构：

[1] Katholieke Univ Leuven, Biochem Neuroendocrinol Lab, Dept Human Genet, B-3000 Leuven, Belgium

[2] Katholieke Univ Leuven, Dept Cellular & Mol Med, Gene Express Unit, B-3000 Leuven, Belgium

[3] Vanderbilt Univ Sch Med, Ctr Stem Cell Biol, Nashville, TN 37232 USA

[4] Vanderbilt Univ Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA

[5] Vrije Univ Brussel, Dept Pharmaceut Chem & Drug Anal, Ctr Neurosci, B-1090 Brussels, Belgium

[6] Univ Paris 05, Sorbonne Paris Cite, Res Ctr Growth & Signaling, INSERM U845,PRL GH Pathophysiol Lab,Fac Med, F-75993 Paris, France

[7] Univ Paris 11, Fac Med Paris Sud, INSERM U693, F-94276 Le Kremlin Bicetre, France

[8] Vrije Univ Brussel, Diabet Res Ctr, B-1090 Brussels, Belgium

来源：

CELL METABOLISM | 2014年 / 20卷 / 06期

关键词：

PANCREATIC BETA-CELLS; NORMAL GLUCOSE-HOMEOSTASIS; INSULIN-SECRETION; PLACENTAL-LACTOGEN; PROLACTIN RECEPTOR; CRE RECOMBINASE; MICE; TRANSPORTER; LANGERHANS; PREGNANCY;

D O I：

10.1016/j.cmet.2014.11.004

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 second-cistron, and thus not thought to be expressed, we found that three commonly used lines, Pdx1-Cre(Late), RIP-Cre, and MIP-GFP, each expressed significant amounts of hGH in pancreatic islets. Locally secreted hGH binds to prolactin receptors on beta cells, activates STAT5 signaling, and induces pregnancy-like changes in gene expression, thereby augmenting pancreatic beta cell mass and insulin content. In addition, islets of Pdx1-Cre(Late) mice have lower GLUT2 expression and reduced glucose-induced insulin release and are protected against the beta cell toxin streptozotocin. These findings may be important when interpreting results obtained when these and other hGH minigene-containing transgenic mice are used.

引用

页码：979 / 990

页数：12

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