Mimic Human Diseases

Cell Deletion Using Suicide Genes

Use of cell ablation techniques enables the ability to delete upon request one cell type of interest from an organism. Cell depletion is a powerful research tool with two main applications:

  • The mimicry of human diseases or drug side effects. Depleting cell populations in vivo can reliably mimic such physio-pathologies (hepatitis, neurodegenerative diseases, etc.).
  • The improvement of xenograft efficiency. It may also be useful to partially or totally remove endogenous cells from the recipient organ / organism.

To this purpose a suicide gene will be targeted using the Humanization & Knockin Technology so that it will only be expressed in the cell type to be deleted. At this stage the suicide gene has no effect on the cell. When a drug specific to the suicide gene used is delivered to the animals, the suicide gene will metabolize the drug creating toxic metabolites resulting in the death of the cells expressing the suicide gene (but not the other cells which do not respond to the drug).

 

Case study: Diphteria toxin-induced cell knockout.

Adapted from Wu et al. Development 2006. Motoneurons and oligodendrocytes are sequentially generated from neural stem cells but do not appear to share common lineage-restricted progenitors in vivo.

Cell Knockout induced by Diphteria toxin

 

Target Cell Population is Killed

Mouse embryo expressing the Diphteria toxin (DT) in Olig1+ cells (Olig1-DTA) show absence of motoneurons.

I, J, M, N) Brain section from a wild-type mouse, showing normal presence of motoneurons.

K, L, O, P) Motoneurons from transgenic mouse expressing DT (Olig1-DTA) are largely missing.