Nucleic Acids Research, Vol 27, Issue 22 4324-4327, Copyright © 1999 by Oxford University Press
AK Indra, X Warot, J Brocard, JM Bornert, JH Xiao, P Chambon and D Metzger
Conditional DNA excision between two LoxP sites can be achieved in the
mouse using Cre-ER(T), a fusion protein between a mutated ligand binding
domain of the human estrogen receptor (ER) and the Cre recombinase, the
activity of which can be induced by 4-hydroxy- tamoxifen (OHT), but not
natural ER ligands. We have recently characterized a new ligand-dependent
recombinase, Cre-ER(T2), which was approximately 4-fold more efficiently
induced by OHT than Cre-ER(T) in cultured cells. In order to compare the in
vivo efficiency of these two ligand-inducible recombinases to generate
temporally-controlled somatic mutations, we have engineered transgenic mice
expressing a LoxP-flanked (floxed) transgene reporter and either Cre-ER(T)
or Cre-ER(T2) under the control of the bovine keratin 5 promoter that is
specifically active in the epidermis basal cell layer. No background
recombinase activity could be detected, while recombination was induced in
basal keratinocytes upon OHT administration. Interestingly, a dose-response
study showed that Cre-ER(T2) was approximately 10-fold more sensitive to
OHT induction than Cre-ER(T).
ARTICLES
Temporally-controlled site-specific mutagenesis in the basal layer of the epidermis: comparison of the recombinase activity of the tamoxifen- inducible Cre-ER(T) and Cre-ER(T2) recombinases
Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP, College de France, BP 163, 67404 Illkirch Cedex, C. U. de Strasbourg, France.
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||||
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