title: TCreERT2, a transgenic mouse line for temporal control of Cre-mediated recombination in lineages emerging from the primitive streak or tail bud.
abstract: The study of axis extension and somitogenesis has been greatly advanced through the use of genetic tools such as the TCre mouse line. In this line, Cre is controlled by a fragment of the T (Brachyury) promoter that is active in progenitor cells that reside within the primitive streak and tail bud and which give rise to lineages emerging from these tissues as the embryonic axis extends. However, because TCre-mediated recombination occurs early in development, gene inactivation can result in an axis truncation that precludes the study of gene function in later or more posterior tissues. To address this limitation, we have generated an inducible TCre transgenic mouse line, called TCreERT2, that provides temporal control, through tamoxifen administration, in all cells emerging from the primitive streak or tail bud throughout development. TCreERT2 activity is mostly silent in the absence of tamoxifen and, in its presence, results in near complete recombination of emerging mesoderm from E7.5 through E13.5. We demonstrate the utility of the TCreERT2 line for determining rate of posterior axis extension and somite formation, thus providing the first in vivo tool for such measurements. To test the usefulness of TCreERT2 for genetic manipulation, we demonstrate that an early deletion of ß-Catenin via TCreERT2 induction phenocopies the TCre-mediated deletion of ß-Catenin defect, whereas a later induction bypasses this early phenotype and produces a similar defect in more caudal tissues. TCreERT2 provides a useful and novel tool for the control of gene expression of emerging embryonic lineages throughout development.
authors: Cancer and Developmental Biology Lab, National Cancer Institute, Frederick, Maryland, United States of America.
authors: Matthew J
authors: MJ
authors: Anderson
authors: L A
authors: LA
authors: Naiche
authors: Catherine P
authors: CP
authors: Wilson
authors: Cindy
authors: C
authors: Elder
authors: Deborah A
authors: DA
authors: Swing
authors: Mark
authors: M
authors: Lewandoski
mesh_terms: D000818:Animals; D004965:Estrogen Antagonists / Q000008:administration & dosage; D005260:Female; D005326:Fetal Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics*; D054240:Primitive Streak / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D011995:Recombination, Genetic; D020825:T-Box Domain Proteins / Q000235:genetics; D013629:Tamoxifen / Q000008:administration & dosage; D000098908:Brachyury Protein
chemical_list: D004965:Estrogen Antagonists; D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D013629:Tamoxifen; D000098908:Brachyury Protein
references: PLoS One. 2009;4(5):e5435
references: 19415111
references: Genesis. 2005 Nov;43(3):148-53
references: 16267823
references: Nature. 2008 Jul 17;454(7202):335-9
references: 18563087
references: EMBO Rep. 2001 Apr;2(4):292-7
references: 11306549
references: Mech Dev. 2000 Mar 1;91(1-2):19-30
references: 10704827
references: Neuron. 2004 Aug 5;43(3):345-57
references: 15294143
references: Dev Cell. 2004 Jan;6(1):7-28
references: 14723844
references: Development. 2009 Apr;136(8):1375-85
references: 19304889
references: Development. 2007 Nov;134(22):4033-41
references: 17965051
references: Dev Genes Evol. 1997 Nov;207(5):330-339
references: 27747430
references: Development. 2001 Apr;128(8):1253-64
references: 11262227
references: Development. 2011 Dec;138(24):5369-78
references: 22110055
references: Mech Dev. 1996 May;56(1-2):139-49
references: 8798154
references: Biochem Biophys Res Commun. 1997 Aug 28;237(3):752-7
references: 9299439
references: BMC Dev Biol. 2009 May 29;9:31
references: 19476657
references: Dev Dyn. 2009 Jan;238(1):123-37
references: 19097117
references: Nat Rev Genet. 2001 Oct;2(10):743-55
references: 11584291
references: Dev Biol. 2010 Aug 15;344(2):669-81
references: 20501333
references: Dev Biol. 2002 Apr 15;244(2):305-18
references: 11944939
references: Development. 2005 Oct;132(19):4235-45
references: 16120640
references: Nat Commun. 2011 Jul 12;2:390
references: 21750544
references: Genesis. 2010 Feb;48(2):73-85
references: 20095055
references: Dev Biol. 2008 Apr 15;316(2):524-37
references: 18328475
references: Development. 2005 Sep;132(17):3859-71
references: 16049111
references: Dev Biol. 2010 May 15;341(2):488-98
references: 20303345
references: Genesis. 2012 Jun;50(6):490-5
references: 22121035
references: Dev Dyn. 1997 Sep;210(1):53-65
references: 9286595
references: J Embryol Exp Morphol. 1981 Oct;65 Suppl:103-28
references: 6801176
references: Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4018-23
references: 21368122
references: Nat Genet. 1999 Jan;21(1):70-1
references: 9916792
references: Cardiovasc Res. 2008 Aug 1;79(3):448-57
references: 18440989
references: Dev Dyn. 2008 Dec;237(12):3591-601
references: 18773491
references: Development. 2008 Feb;135(3):501-11
references: 18171685
references: Development. 2002 Oct;129(20):4855-66
references: 12361976
references: Dev Biol. 2011 Mar 15;351(2):254-65
references: 21256124
references: Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8668-73
references: 11447280
references: Methods Mol Biol. 2009;530:343-63
references: 19266339
references: Genesis. 2009 May;47(5):309-13
references: 19298012
references: Handb Exp Pharmacol. 2007;(178):235-62
references: 17203658
references: Genes Dev. 1999 Dec 15;13(24):3185-90
references: 10617567
references: Nat Cell Biol. 2008 Feb;10(2):186-93
references: 18157121
references: Cold Spring Harb Symp Quant Biol. 1997;62:159-68
references: 9598348
references: Development. 2008 Jan;135(1):85-94
references: 18045842