3.7 A Very Interesting Transgenic Mouse for Neuroscience

One of the very exciting aspects of neuroscience is the use of transgenic mice to aid in our understanding of behaviour. One particular mouse, not originally intended for use in neuroscience was the Rosa or iDTR mouse. The Rosa or iDTR (inducible Diphtheria Toxin Receptor) mouse utilizes a transgene very similar to the Cre-driver lines. In this mouse (shown in Figure 1) all cells throughout the mouse’s body carry the DNA sequence for the Diphtheria Toxin Receptor (DTR). Note that this DTR DNA sequence is preceded by a STOP codon that is flanked by loxP sites. If Cre-recombinase was introduced by vector injection then the STOP codon is removed and the DTR is now transcribed and translated in the area or tissue where the Cre-recombinase was injected. Normally, this does not present a problem as the mouse has had no exposure to diphtheria toxin. However, we can inject the toxin systemically into the mouse and only those cells expressing the receptor will undergo apoptotic cell death.

Schematic diagram illustrating the concept of using the Rosa/iDTR mouse to eliminate specific groups of cells. Much like the Cre-Lox system, there is a reliance on driver lines. All cells in the mouse's body carries the DNA sequence for Diptheria Toxin Receptor(DTR). However, due to the STOP codon being upstream of the DTR, the DTR is never transcribed. However, when a vector is injected into the mouse, the LoxPs excise the STOP codon and thus DTR is able to be transcribed and translated in the tissue where Cre-recombinase was injected. When injected with the diptheria toxin, the cells are able to accept it with the expressed DTR and thus undergo apoptosis.
Figure 1. Schematic diagram illustrating the concept of using the Rosa/iDTR mouse to eliminate specific groups of cells. Much like the Cre-Lox system, there is a reliance on driver lines. All cells in the mouse’s body carry the DNA sequence for Diptheria Toxin Receptor(DTR). However, due to the STOP codon being upstream of the DTR, the DTR is never transcribed. However, when a vector is injected into the mouse, the LoxPs excise the STOP codon and thus DTR is able to be transcribed and translated in the tissue where Cre-recombinase was injected. When injected with the Diptheria toxin, the cells are able to bind it with the expressed DTR and thus undergo apoptosis.

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Neuroscience: Canadian 2nd Edition Open Textbook Copyright © 2020 by Dr William Ju is licensed under a Creative Commons Attribution 4.0 International License, except where otherwise noted.

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