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Inducible site‐specific recombination in myelinating cells
Author(s) -
Doerflinger Nathalie H.,
Macklin Wendy B.,
Popko Brian
Publication year - 2003
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/gene.10154
Subject(s) - biology , cre recombinase , microbiology and biotechnology , fusion protein , proteolipid protein 1 , oligodendrocyte , myelin basic protein , transgene , gene , myelin , genetically modified mouse , genetics , recombinant dna , central nervous system , neuroscience
Abstract Summary: 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 (CreER T ) to obtain inducible, site‐specific recombination. CreER T 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 CreER T fusion protein translocated to the nucleus and mediated the recombination of a LacZ reporter transgene in myelinating cells of PLP/CreER T mice injected with the synthetic steroid tamoxifen. In untreated animals CreER T remained cytoplasmic, and there was no evidence of recombination. The PLP/ CreER T 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. genesis 35:63–72, 2003. © 2002 Wiley‐Liss, Inc.