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Kaklamanos, A.* ; Rozman, J. ; Roulis, M.* ; Karagianni, N.* ; Armaka, M.* ; Wu, M. ; Brachthäuser, L. ; Calzada-Wack, J. ; Horsch, M. ; Beckers, J. ; Rathkolb, B. ; Adler, T. ; Neff, F. ; Wolf, E.* ; Gailus-Durner, V. ; Fuchs, H. ; Hrabě de Angelis, M. ; Kollias, G.*

Extensive phenotypic characterization of a new transgenic mouse reveals pleiotropic perturbations in physiology due to mesenchymal hGH minigene expression.

Sci. Rep. 7:2397 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The human growth hormone (hGH) minigene used for transgene stabilization in mice has been recently identified to be locally expressed in the tissues where transgenes are active and associated with phenotypic alterations. Here we extend these findings by analyzing the effect of the hGH minigene in TgC6hp55 transgenic mice which express the human TNFR1 under the control of the mesenchymal cell-specific CollagenVI promoter. These mice displayed a fully penetrant phenotype characterized by growth enhancement accompanied by perturbations in metabolic, skeletal, histological and other physiological parameters. Notably, this phenotype was independent of TNF-TNFR1 signaling since the genetic ablation of either Tnf or Tradd did not rescue the phenotype. Further analyses showed that the hGH minigene was expressed in several tissues, also leading to increased hGH protein levels in the serum. Pharmacological blockade of GH signaling prevented the development of the phenotype. Our results indicate that the unplanned expression of the hGH minigene in CollagenVI expressing mesenchymal cells can lead through local and/or systemic mechanisms to enhanced somatic growth followed by a plethora of primary and/or secondary effects such as hyperphagia, hypermetabolism, disturbed glucose homeostasis, altered hematological parameters, increased bone formation and lipid accumulation in metabolically critical tissues.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Human Growth-hormone; Pancreatic Beta-cells; Factor-i; Inflammatory Responses; Gene-expression; Cre Recombinase; Bone-growth; Stem-cells; Dwarf Mice; Tnf-alpha
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Journal Scientific Reports
Quellenangaben Volume: 7, Issue: 1, Pages: , Article Number: 2397 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Institute of Pathology (PATH)