Ectopic correction of ornithine transcarbamylase deficiency in sparse fur mice

Stephen N. Jones, Markus Grompe, M. Idrees Munir, Gabor Veres, William J. Craigen, C. Thomas Caskey

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The sparse fur (spf) mutant mouse is a model for human X-linked ornithine transcarbamylase (OTC) deficiency. Human OTC cDNA placed under transcriptional control of the mouse OTC promoter was microinjected into fertilized oocytes of spf mice. Two founder lines of transgenic mice were phenotypically and biochemically corrected for OTC deficiency by the expression of the human gene at high levels in the small intestine with little or no expression occurring in the liver. The tissue pattern of expression of transgenic mice bearing the chloramphenicol acetyltransferase gene placed under the control of the mouse OTC promoter parallels these results. These experiments demonstrate that human OTC cDNA is selectively expressed in small bowel by a truncated OTC promoter, and such ectopic expression corrects the sp/phenotypic and metabolic features of this inborn error. These data suggest that somatic gene therapy of OTC deficiency can be achieved by intestine-targeted gene transfer.

Original languageEnglish (US)
Pages (from-to)14684-14690
Number of pages7
JournalJournal of Biological Chemistry
Volume265
Issue number24
StatePublished - Aug 25 1990
Externally publishedYes

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Ornithine Carbamoyltransferase Deficiency Disease
Ornithine Carbamoyltransferase
Transgenic Mice
Complementary DNA
Chloramphenicol O-Acetyltransferase
Bearings (structural)
Genes
Genetic Therapy
Small Intestine
Oocytes
Intestines
Gene transfer
Gene therapy
Gene Expression
Liver
Tissue

ASJC Scopus subject areas

  • Biochemistry

Cite this

Jones, S. N., Grompe, M., Munir, M. I., Veres, G., Craigen, W. J., & Caskey, C. T. (1990). Ectopic correction of ornithine transcarbamylase deficiency in sparse fur mice. Journal of Biological Chemistry, 265(24), 14684-14690.

Ectopic correction of ornithine transcarbamylase deficiency in sparse fur mice. / Jones, Stephen N.; Grompe, Markus; Munir, M. Idrees; Veres, Gabor; Craigen, William J.; Caskey, C. Thomas.

In: Journal of Biological Chemistry, Vol. 265, No. 24, 25.08.1990, p. 14684-14690.

Research output: Contribution to journalArticle

Jones, SN, Grompe, M, Munir, MI, Veres, G, Craigen, WJ & Caskey, CT 1990, 'Ectopic correction of ornithine transcarbamylase deficiency in sparse fur mice', Journal of Biological Chemistry, vol. 265, no. 24, pp. 14684-14690.
Jones SN, Grompe M, Munir MI, Veres G, Craigen WJ, Caskey CT. Ectopic correction of ornithine transcarbamylase deficiency in sparse fur mice. Journal of Biological Chemistry. 1990 Aug 25;265(24):14684-14690.
Jones, Stephen N. ; Grompe, Markus ; Munir, M. Idrees ; Veres, Gabor ; Craigen, William J. ; Caskey, C. Thomas. / Ectopic correction of ornithine transcarbamylase deficiency in sparse fur mice. In: Journal of Biological Chemistry. 1990 ; Vol. 265, No. 24. pp. 14684-14690.
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