Developmental regulation of α-fetoprotein genes in transgenic mice

R. Krumlauf, Robert E Hammer, S. M. Tilghman, R. L. Brinster

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

The mouse α-fetoprotein gene is activated in embryonic development in the visceral endoderm of the extraembryonic yolk sac and the fetal liver and gut. Transcription of the gene is subsequently repressed in the neonatal liver. To ask whether the DNA sequence elements required for tissue-specific activation are the same or different from those required for fetal postnatal developmental regulation of the gene, modified copies of the α-fetoprotein gene were microinjected into fertilized mouse eggs. Those animals which developed to term and carried integrated copies of the modified gene were analyzed for expression. In approximately 50% of such animals, the introduced gene was active only in three cell lineages which expressed the authentic α-fetoprotein gene. Furthermore, its expression was repressed in the neonatal liver. Thus, we conclude that the modified genes, which included either 7 or 14 kilobase pairs of 5'-flanking DNA, contained the DNA sequence information to direct both tissue-specific expression and developmental regulation. The observation that 50% of the mice which carried the modified gene did not express it in any tissue, combined with the fact that the level of expression was highly variable between expressing transgenic animals, suggested that the gene was susceptible to its site of integration in the mouse genome.

Original languageEnglish (US)
Pages (from-to)1639-1648
Number of pages10
JournalMolecular and Cellular Biology
Volume5
Issue number7
StatePublished - 1985

Fingerprint

Fetal Proteins
Transgenic Mice
Genes
Liver
Developmental Genes
Yolk Sac
Endoderm
Genetically Modified Animals
Zygote
Cell Lineage
Embryonic Development
Genome

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Krumlauf, R., Hammer, R. E., Tilghman, S. M., & Brinster, R. L. (1985). Developmental regulation of α-fetoprotein genes in transgenic mice. Molecular and Cellular Biology, 5(7), 1639-1648.

Developmental regulation of α-fetoprotein genes in transgenic mice. / Krumlauf, R.; Hammer, Robert E; Tilghman, S. M.; Brinster, R. L.

In: Molecular and Cellular Biology, Vol. 5, No. 7, 1985, p. 1639-1648.

Research output: Contribution to journalArticle

Krumlauf, R, Hammer, RE, Tilghman, SM & Brinster, RL 1985, 'Developmental regulation of α-fetoprotein genes in transgenic mice', Molecular and Cellular Biology, vol. 5, no. 7, pp. 1639-1648.
Krumlauf, R. ; Hammer, Robert E ; Tilghman, S. M. ; Brinster, R. L. / Developmental regulation of α-fetoprotein genes in transgenic mice. In: Molecular and Cellular Biology. 1985 ; Vol. 5, No. 7. pp. 1639-1648.
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