Developmental regulation of a complete 70-kb human beta-globin locus in transgenic mice

J Strouboulis, N Dillon, F Grosveld

Research output: Contribution to journalArticlepeer-review

186 Citations (Scopus)

Abstract

We have used a linker-based ligation strategy to combine two 35-kb cosmid inserts from the human beta-globin locus into one linear fragment containing the entire locus. This 70-kb fragment was introduced into transgenic mice by microinjection of fertilized eggs. Southern blot analysis showed that a single complete transgene locus can be introduced into the germ line with high efficiency. Analysis of the expression patterns of the locus during development shows that the epsilon-globin gene behaves as a purely embryonic gene, the gamma-globin gene as an embryonic and early fetal gene, and the beta-globin gene as a fetal adult gene. Quantitation of expression showed that the levels of transcription of the epsilon- and gamma-globin genes are reversed relative to their mouse homologs but that the total output of the human and mouse loci is constant during development. These results suggest that multiple changes in DNA sequences and transcription factor balance must have occurred for the human gamma-globin gene to have evolved into a fetal gene.

Original languageEnglish
Pages (from-to)1857-64
Number of pages8
JournalGenes and Development
Volume6
Issue number10
DOIs
Publication statusPublished - Oct 1992

Keywords

  • Animals
  • Base Sequence
  • Blotting, Southern
  • Cosmids
  • Gene Expression Regulation
  • Globins/genetics
  • Humans
  • Liver/embryology
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • RNA/genetics
  • Transcription, Genetic

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