Evaluation of the transfer and expression in mice of an enzyme-encoding gene using a human adenovirus vector
- PMID: 2081192
- DOI: 10.1089/hum.1990.1.3-241
Evaluation of the transfer and expression in mice of an enzyme-encoding gene using a human adenovirus vector
Abstract
Mutant mice of the Spf-ash strain have an inherited defect in ornithine transcarbamylase (OTC) protein synthesis, and were used to ascertain the potential of recombinant adenoviruses for introducing and expressing the normal gene lacking in these mice. These OTC mutant mice are characterized by a reduction in the amount of OTC activity, resulting in hyperammonemia, pronounced orotic aciduria, growth retardation, and sparse fur until weaning. A recombinant adenovirus that harbors the rat OTC cDNA under the control of the viral major late promoter (MLP) was constructed and injected into such newborn mice. The effect of the virus was analyzed by monitoring the hepatic OTC enzyme during several months after the injection. An increase in OTC activity was detected and was accompanied by a diminution of orotic acid in the urine. The observation of MLP-OTC mRNA transcripts over 1 year following the injection attests to the relatively long-term presence of the transferred gene. In those mice showing the greatest OTC activity, a normalization of the fur was also observed. The experiments reported here document the feasibility of using adenovirus for the direct delivery in vivo of a gene to restore an impaired metabolism.
Similar articles
-
Correction of ornithine transcarbamylase deficiency in adult spf(ash) mice and in OTC-deficient human hepatocytes with recombinant adenoviruses bearing the CAG promoter.Hum Gene Ther. 1996 May 1;7(7):821-30. doi: 10.1089/hum.1996.7.7-821. Hum Gene Ther. 1996. PMID: 8860834
-
Efficient mitochondrial import of newly synthesized ornithine transcarbamylase (OTC) and correction of secondary metabolic alterations in spf(ash) mice following gene therapy of OTC deficiency.Mol Med. 1999 Apr;5(4):244-53. Mol Med. 1999. PMID: 10448647 Free PMC article.
-
Retroviral-mediated gene transfer of human ornithine transcarbamylase into primary hepatocytes of spf and spf-ash mice.Hum Gene Ther. 1992 Feb;3(1):35-44. doi: 10.1089/hum.1992.3.1-35. Hum Gene Ther. 1992. PMID: 1562638
-
Gene therapy for ornithine transcarbamylase deficiency.Acta Paediatr Jpn. 1996 Apr;38(2):189-92. doi: 10.1111/j.1442-200x.1996.tb03467.x. Acta Paediatr Jpn. 1996. PMID: 8677801 Review.
-
Comprehensive characterization of ureagenesis in the spfash mouse, a model of human ornithine transcarbamylase deficiency, reveals age-dependency of ammonia detoxification.J Inherit Metab Dis. 2019 Nov;42(6):1064-1076. doi: 10.1002/jimd.12068. Epub 2019 Mar 13. J Inherit Metab Dis. 2019. PMID: 30714172 Review.
Cited by
-
Adenovirus-mediated transfer of low density lipoprotein receptor gene acutely accelerates cholesterol clearance in normal mice.Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2812-6. doi: 10.1073/pnas.90.7.2812. Proc Natl Acad Sci U S A. 1993. PMID: 8464893 Free PMC article.
-
Adenovirus-mediated gene transfer into striated muscles.J Mol Med (Berl). 1995 Apr;73(4):165-80. doi: 10.1007/BF00188137. J Mol Med (Berl). 1995. PMID: 7627637 Review. No abstract available.
-
Disappearance of body fat in normal rats induced by adenovirus-mediated leptin gene therapy.Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14795-9. doi: 10.1073/pnas.93.25.14795. Proc Natl Acad Sci U S A. 1996. PMID: 8962134 Free PMC article.
-
High-efficiency receptor-mediated delivery of small and large (48 kilobase gene constructs using the endosome-disruption activity of defective or chemically inactivated adenovirus particles.Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6094-8. doi: 10.1073/pnas.89.13.6094. Proc Natl Acad Sci U S A. 1992. PMID: 1352882 Free PMC article.
-
The influence of innate and pre-existing immunity on adenovirus therapy.J Cell Biochem. 2009 Nov 1;108(4):778-90. doi: 10.1002/jcb.22328. J Cell Biochem. 2009. PMID: 19711370 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
