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 language | English |
|---|---|
| Pages (from-to) | 7636-7642 |
| Number of pages | 7 |
| Journal | Molecular and Cellular Biology |
| Volume | 24 |
| Issue number | 17 |
| DOIs | |
| Publication status | Published - Sep 2004 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cell Biology
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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 journal › Article
}
TY - JOUR
T1 - Cell depletion due to diphtheria toxin fragment A after Cre-mediated recombination
AU - Brockschnieder, Damian
AU - Lappe-Siefke, Corinna
AU - Goebbels, Sandra
AU - Boesl, Michael R.
AU - Nave, Klaus Armin
AU - Riethmacher, Dieter
PY - 2004/9
Y1 - 2004/9
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.24.17.7636-7642.2004
DO - 10.1128/MCB.24.17.7636-7642.2004
M3 - Article
VL - 24
SP - 7636
EP - 7642
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 17
ER -