Construction and in vivo efficacy of a replication-deficient recombinant adenovirus encoding murine growth hormone.
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 i.m. 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 i.v. 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.
Marmary
Y
Y
Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, Maryland 20892, USA.
Parlow
A F
AF
Goldsmith
C M
CM
He
X
X
Wellner
R B
RB
Satomura
K
K
Kriete
M F
MF
Robey
P G
PG
Nieman
L K
LK
Baum
B J
BJ
D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D002875:Chromosomes; D004268:DNA-Binding Proteins / Q000235:genetics; D018014:Gene Transfer Techniques; D013006:Growth Hormone / Q000235:genetics* / Q000494:pharmacology*; D007273:Injections, Intramuscular; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects; D010908:Pituitary Hormones, Anterior / Q000096:biosynthesis / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D013363:Submandibular Gland / Q000187:drug effects; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics; D014779:Virus Replication
D004268:DNA-Binding Proteins; D013006:Growth Hormone; D010908:Pituitary Hormones, Anterior; D011994:Recombinant Proteins; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C494185:Pou1f1 protein, mouse; C494186:Pou1f1 protein, rat