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Construction and in Vivo Efficacy of a Replication-Deficient Recombinant Adenovirus Encoding Murine Growth Hormone

Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research (Y.M., C.M.G., X.H., R.B.W., B.J.B.), Bethesda, Maryland 20892; National Hormone and Pituitary Program, Harbor-UCLA Medical Center (A.F.P.), Torrance, California 90509; Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research (K.S., P.G.R.); Animal Care Unit, National Institute of Dental and Craniofacial Research (M.F.K.); and Developmental Endocrinology Branch, National Institute of Child Health and Human Development (L.K.N.), Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Dr. Bruce J. Baum, Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 10 Center Drive, MSC-1190, Building 10, Room 1N-113, Bethesda, Maryland 20892. E-mail: bruce_j_baum{at}nih.gov

We have constructed a recombinant, replication-deficient, first-generation adenovirus-encoding mouse GH (mGH), AdCMVmGH. This virus directed mGH production from an epithelial cell line in vitro in a dose-dependent manner. When injected into the quadriceps muscle or submandibular ducts of mGH-deficient Snell dwarf mice, AdCMVmGH resulted in the production of significantly elevated serum mGH levels. Furthermore, after im injection, dwarf mice increased in weight by 8% over 4 days and close to 100% by 30 days. When AdCMVmGH was administered to 3- to 4-week-old rats by iv injection to assess general metabolic responses, serum mGH, insulin-like growth factor 1, triglycerides and cholesterol levels were significantly elevated. AdCMVmGH should be a valuable experimental tool for the controlled, directed expression of mGH in preclinical mouse model studies.

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