An improved mouse line for Cre-induced cell ablation due to diphtheria toxin A, expressed from the Rosa26 locus

Damian Brockschnieder, Yvonne Pechmann, Eva Sonnenberg-Riethmacher, Dieter Riethmacher

Research output: Contribution to journalArticle

74 Citations (Scopus)

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 lacZfloxDT-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 lacZfloxDTA allele, as exemplified by the complete ablation of oligodendrocytes upon Cre-mediated recombination. The novel R26:lacZbpAfloxDTA line is expected to greatly facilitate the reliable generation of cell type ablated mice.

Original languageEnglish
Pages (from-to)322-327
Number of pages6
JournalGenesis
Volume44
Issue number7
DOIs
Publication statusPublished - Jul 2006
Externally publishedYes

Fingerprint

Diphtheria Toxin
Genetic Recombination
Alleles
Polyadenylation
Oligodendroglia
Open Reading Frames

Keywords

  • Cell ablation
  • Cre recombinase
  • Diphtheria toxin
  • Oligodendrocytes
  • Rosa26

ASJC Scopus subject areas

  • Genetics

Cite this

An improved mouse line for Cre-induced cell ablation due to diphtheria toxin A, expressed from the Rosa26 locus. / Brockschnieder, Damian; Pechmann, Yvonne; Sonnenberg-Riethmacher, Eva; Riethmacher, Dieter.

In: Genesis, Vol. 44, No. 7, 07.2006, p. 322-327.

Research output: Contribution to journalArticle

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