Cell depletion due to diphtheria toxin fragment A after Cre-mediated recombination

Damian Brockschnieder, Corinna Lappe-Siefke, Sandra Goebbels, Michael R. Boesl, Klaus Armin Nave, Dieter Riethmacher

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Abnormal cell loss is the common cause of a large number of developmental and degenerative diseases. To model such diseases in transgenic animals, we have developed a line of mice that allows the efficient depletion of virtually any cell type in vivo following somatic Cre-mediated gene recombination. By introducing the diphtheria toxin fragment A (DT-A) gene as a conditional expression construct (floxed lacZ-DT-A) into the ubiquitously expressed ROSA26 locus, we produced a line of mice that would permit cell-specific activation of the toxin gene. Following Cre-mediated recombination under the control of cell-type-specific promoters, lacZ gene expression was efficiently replaced by de novo transcription of the Cre-recombined DT-A gene. We provide proof of this principle, initially for cells of the central nervous system (pyramidal neurons and oligodendrocytes), the immune system (B cells), and liver tissue (hepatocytes), that the conditional expression of DT-A is functional in vivo, resulting in the generation of novel degenerative disease models.

Original languageEnglish
Pages (from-to)7636-7642
Number of pages7
JournalMolecular and Cellular Biology
Volume24
Issue number17
DOIs
Publication statusPublished - Sep 2004
Externally publishedYes

Fingerprint

Genetic Recombination
Genes
Genetically Modified Animals
Lac Operon
Pyramidal Cells
Oligodendroglia
Transcriptional Activation
Hepatocytes
Immune System
B-Lymphocytes
Central Nervous System
diphtheria toxin fragment A
Gene Expression
Liver

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Cell depletion due to diphtheria toxin fragment A after Cre-mediated recombination. / Brockschnieder, Damian; Lappe-Siefke, Corinna; Goebbels, Sandra; Boesl, Michael R.; Nave, Klaus Armin; Riethmacher, Dieter.

In: Molecular and Cellular Biology, Vol. 24, No. 17, 09.2004, p. 7636-7642.

Research output: Contribution to journalArticle

Brockschnieder, Damian ; Lappe-Siefke, Corinna ; Goebbels, Sandra ; Boesl, Michael R. ; Nave, Klaus Armin ; Riethmacher, Dieter. / Cell depletion due to diphtheria toxin fragment A after Cre-mediated recombination. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 17. pp. 7636-7642.
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