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This Article Full Text Full Text (PDF) All Versions of this Article: 285/2/E427    most recent 00573.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Søndergaard, M. Articles by Jensen, T. G. Search for Related Content PubMed PubMed Citation Articles by Søndergaard, M. Articles by Jensen, T. G.

Normalization of growth in hypophysectomized mice using hydrodynamic transfer of the human growth hormone gene

Department of ¹Human Genetics and ²Medical Microbiology and Immunology, ³Medical Research Laboratories and Medical Department of Diabetes and Endocrinology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark

Submitted 27 December 2002 ; accepted in final form 12 March 2003

Nonviral gene transfer was investigated as a potential treatment of growth hormone deficiency (GHD) using hypophysectomized mice as a model. After a single hydrodynamic administration of naked plasmid DNA containing the human growth hormone (hGH) gene controlled by an ubiquitin promoter, sustained elevation of circulating hGH was observed the entire observation period (68 days), with a concomitant normalization of circulating insulin-like growth factor I (IGF-I) and IGF-binding protein-3. Furthermore, longitudinal growth was corrected in terms of normalization of tibia length, tail length, and body weight gain. Liver, spleen, and lung weights were normalized, whereas heart weight was normalized partly. hGH mRNA was expressed exclusively in liver tissue. In conclusion, we showed that nonviral hGH gene transfer normalizes longitudinal growth in hypophysectomized mice, indicating that this method potentially could be relevant as a new therapeutic tool in the clinical handling of GHD.

nonviral gene therapy; insulin-like growth factor I; insulin-like growth factor-binding protein-3; ubiquitin promotor; growth hormone deficiency

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