Nucleic Acids Research, Vol 26, Issue 6 1427-1432, Copyright © 1998 by Oxford University Press
F Schwenk, R Kuhn, PO Angrand, K Rajewsky and AF Stewart
In mice transgenesis through oocyte injection or DNA recombination in
embryonal stem (ES) cells allows mutations to be introduced into the
germline. However, the earliest phenotype of the introduced mutation can
eclipse later effects. We show in mice that site-specific genomic
recombination can be induced in a selected cell type, B lymphocytes, at a
chosen time. This precision of somatic mutagenesis was accomplished by
limiting expression of a Cre recombinase-estrogen receptor fusion protein
to B lymphocytes by use of tissue-specific elements in the promoter of the
transgene employed. The expressed fusion protein remained inactive until
derepressed by systemic administration of an exogenous ligand for the
estrogen receptor, 4-OH-tamoxifen. Upon derepression the Cre recombinase
enzyme deleted specific DNA segments, flanked by loxP sites, in B
lymphocytes only. The efficiency of recombination in cells expressing the
fusion protein could be varied from low levels to >80%, depending on the
dose of ligand administered. Our work presents a paradigm applicable to
other uses of site-specific recombination in somatic mutagenesis where both
temporal and spatial regulation are desired.
ARTICLES
Temporally and spatially regulated somatic mutagenesis in mice
Institute for Genetics, University of Cologne, Weyertal 121, 50931 Cologne, Germany.
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