Inducible site-specific recombination in myelinating cells

Nathalie H. Doerflinger, Wendy B. Macklin, Brian Popko*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

160 Scopus citations

Abstract

To explore the function of genes expressed by myelinating cells we have developed a model system that allows for the inducible ablation of predetermined genes in oligodendrocytes and Schwann cells. The Cre/loxP recombination system provides the opportunity to generate tissue-specific somatic mutations in mice. We have used a fusion protein between the Cre recombinase and a mutated ligand-binding domain of the human estrogen receptor (CreERT) to obtain inducible, site-specific recombination. CreERT expression was placed under the transcriptional control of the regulatory sequences of the myelin proteolipid protein (PLP) gene, which is abundantly expressed in oligodendrocytes and to a lesser extent in Schwann cells. The CreERT fusion protein translocated to the nucleus and mediated the recombination of a LacZ reporter transgene in myelinating cells of PLP/CreERT mice injected with the synthetic steroid tamoxifen. In untreated animals CreERT remained cytoplasmic, and there was no evidence of recombination. The PLP/CreERT animals should be very useful in elucidating and distinguishing a particular gene's function in the formation and maintenance of the myelin sheath and in analyzing mature oligodendrocyte function in pathological conditions.

Original languageEnglish (US)
Pages (from-to)63-72
Number of pages10
JournalGenesis
Volume35
Issue number1
DOIs
StatePublished - Jan 1 2003

Keywords

  • CreER
  • Myelinating cells
  • Recombination

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Cell Biology

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