An improved mouse line for Cre-induced cell ablation due to diphtheria toxin A, expressed from the Rosa26 locus
- PMID: 16791847
- DOI: 10.1002/dvg.20218
An improved mouse line for Cre-induced cell ablation due to diphtheria toxin A, expressed from the Rosa26 locus
Abstract
The means to specifically ablate cells inside of a living organism have recently been improved and facilitated by stable mouse lines, carrying conditional expression constructs for diphtheria toxin (DT) or diphtheria toxin receptor, that could be activated upon Cre-mediated recombination or the application of diphtheria toxin, respectively. We have lately described the R26:lacZ/DT-A line (Brockschnieder et al., 2004, Mol Cell Biol 24:7636-7642) in which a loxP-conditional DTA allele was introduced into the ubiquitously expressed Rosa26 locus. This strain allowed the ablation of a wide spectrum of cell types by crossing it to tissue specific Cre lines. Unexpectedly, homozygous (but not heterozygous) animals of the R26:lacZ/DT-A line developed some degenerative abnormalities in a variety of tissues. The defects were most probably caused by leaky expression of small amounts of toxin from the unrecombined lacZ(flox)DT-A cassette. Here we show that insertion of an additional transcriptional regulatory sequence (bovine growth hormone polyadenylation signal, bpA) following the lacZ open reading frame prevented the formation of any defects in homozygous mice. The modification did not affect the functionality of the lacZ(flox)DTA allele, as exemplified by the complete ablation of oligodendrocytes upon Cre-mediated recombination. The novel R26:lacZbpA(flox)DTA line is expected to greatly facilitate the reliable generation of cell type ablated mice.
(c) 2006 Wiley-Liss, Inc.
Similar articles
-
A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration.Nat Methods. 2005 Jun;2(6):419-26. doi: 10.1038/nmeth762. Nat Methods. 2005. PMID: 15908920
-
Cell depletion due to diphtheria toxin fragment A after Cre-mediated recombination.Mol Cell Biol. 2004 Sep;24(17):7636-42. doi: 10.1128/MCB.24.17.7636-7642.2004. Mol Cell Biol. 2004. PMID: 15314171 Free PMC article.
-
Lineage-specific cell disruption in living mice by Cre-mediated expression of diphtheria toxin A chain.Biochem Biophys Res Commun. 2004 Aug 20;321(2):275-9. doi: 10.1016/j.bbrc.2004.06.139. Biochem Biophys Res Commun. 2004. PMID: 15358172
-
Genetic cell ablation.Methods Mol Biol. 2014;1092:421-36. doi: 10.1007/978-1-60327-292-6_25. Methods Mol Biol. 2014. PMID: 24318834 Review.
-
Versatile cell ablation tools and their applications to study loss of cell functions.Cell Mol Life Sci. 2019 Dec;76(23):4725-4743. doi: 10.1007/s00018-019-03243-w. Epub 2019 Jul 29. Cell Mol Life Sci. 2019. PMID: 31359086 Free PMC article. Review.
Cited by
-
Moderate beta-cell ablation triggers synergic compensatory mechanisms even in the absence of overt metabolic disruption.Commun Biol. 2024 Jul 9;7(1):833. doi: 10.1038/s42003-024-06527-5. Commun Biol. 2024. PMID: 38982170 Free PMC article.
-
Nkx2.1-derived astrocytes and neurons together with Slit2 are indispensable for anterior commissure formation.Nat Commun. 2015 Apr 23;6:6887. doi: 10.1038/ncomms7887. Nat Commun. 2015. PMID: 25904499 Free PMC article.
-
An Efficient and Versatile System for Visualization and Genetic Modification of Dopaminergic Neurons in Transgenic Mice.PLoS One. 2015 Aug 20;10(8):e0136203. doi: 10.1371/journal.pone.0136203. eCollection 2015. PLoS One. 2015. PMID: 26291828 Free PMC article.
-
Functions of Murine Dendritic Cells.Immunity. 2016 Oct 18;45(4):719-736. doi: 10.1016/j.immuni.2016.10.010. Immunity. 2016. PMID: 27760337 Free PMC article. Review.
-
Transient callosal projections of L4 neurons are eliminated for the acquisition of local connectivity.Nat Commun. 2019 Oct 7;10(1):4549. doi: 10.1038/s41467-019-12495-w. Nat Commun. 2019. PMID: 31591398 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
