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Tissue- and development-specific expression of the human phenylalanine hydroxylase/chloramphenicol acetyltransferase fusion gene in transgenic mice.

Publication ,  Journal Article
Wang, Y; DeMayo, JL; Hahn, TM; Finegold, MJ; Konecki, DS; Lichter-Konecki, U; Woo, SL
Published in: J Biol Chem
July 25, 1992

Human phenylalanine hydroxylase (PAH) catalyzes the conversion of L-phenylalanine to L-tyrosine. Deficiency of this enzyme results in phenylketonuria, a common genetic disorder of amino acid metabolism that causes severe mental retardation. In primates, PAH is expressed specifically in the liver, while in rodents PAH activity is also present in kidney, although at a much lower level. A 9-kilobase genomic DNA fragment at the 5' end of the hPAH gene (hPAH) was fused to the bacterial chloramphenicol acetyltransferase (CAT) gene. The hPAH/CAT minigene was used to generate multiple transgenic mouse lines. In all expressing lines, CAT activity was detected predominantly in the liver and at much lower levels in the kidney. By immunohistochemical staining, CAT expression was localized to hepatocytes and renal epithelial cells, both of which also express the endogenous mouse PAH enzyme. Furthermore, both the transgene and the endogenous mouse PAH were activated at about the same stage of embryonic development in the mouse liver. These results suggest that the 9-kilobase DNA fragment flanking the 5' end of the human PAH gene contains all the necessary cis-acting elements to direct tissue- and developmental-specific expression in vivo.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

July 25, 1992

Volume

267

Issue

21

Start / End Page

15105 / 15110

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Recombinant Fusion Proteins
  • Phenylalanine Hydroxylase
  • Mice, Transgenic
  • Mice
  • Liver Neoplasms
  • Liver
  • Immunohistochemistry
  • Humans
  • Gene Expression Regulation, Enzymologic
 

Citation

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Wang, Y., DeMayo, J. L., Hahn, T. M., Finegold, M. J., Konecki, D. S., Lichter-Konecki, U., & Woo, S. L. (1992). Tissue- and development-specific expression of the human phenylalanine hydroxylase/chloramphenicol acetyltransferase fusion gene in transgenic mice. J Biol Chem, 267(21), 15105–15110.
Wang, Y., J. L. DeMayo, T. M. Hahn, M. J. Finegold, D. S. Konecki, U. Lichter-Konecki, and S. L. Woo. “Tissue- and development-specific expression of the human phenylalanine hydroxylase/chloramphenicol acetyltransferase fusion gene in transgenic mice.J Biol Chem 267, no. 21 (July 25, 1992): 15105–10.
Wang Y, DeMayo JL, Hahn TM, Finegold MJ, Konecki DS, Lichter-Konecki U, et al. Tissue- and development-specific expression of the human phenylalanine hydroxylase/chloramphenicol acetyltransferase fusion gene in transgenic mice. J Biol Chem. 1992 Jul 25;267(21):15105–10.
Wang Y, DeMayo JL, Hahn TM, Finegold MJ, Konecki DS, Lichter-Konecki U, Woo SL. Tissue- and development-specific expression of the human phenylalanine hydroxylase/chloramphenicol acetyltransferase fusion gene in transgenic mice. J Biol Chem. 1992 Jul 25;267(21):15105–15110.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

July 25, 1992

Volume

267

Issue

21

Start / End Page

15105 / 15110

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Recombinant Fusion Proteins
  • Phenylalanine Hydroxylase
  • Mice, Transgenic
  • Mice
  • Liver Neoplasms
  • Liver
  • Immunohistochemistry
  • Humans
  • Gene Expression Regulation, Enzymologic