Table 1.
Examples of DTx-based mouse models targeting neurons or glia of the central nervous system.
| Mice Expressing DTR | DTx Dosing and Schedules | DTx Effects | Reference |
|---|---|---|---|
| Dopaminergic neurons: DAT-DTR (Slc6a3DTR/+) | 50 ng/g DTx s.c. at the age of 3–5 days DTx: List Biological Laboratories |
Loss of TH+ neurons. Impaired cognition with deficits in spatial learning, spatial memory and object recognition. Impaired motor coordination on balance beam and rotarod |
[44] |
| Doublecortin-positive neurons: DCX-DTR generated by insertion of DTR via homologous recombination |
10 ng/g DTx per day for 10 d i.p. | Deficits of spatial learning and reversal learning | [45] |
| Oligodendroglia: MOG-Cre; Rosa26 loxP-STOP-loxP DTR (= R26-LSL-DTR) | 100 ng DTx per mouse (≈4 ng/g) 1 × daily for 3 d, and 3 × daily for 7 d |
DTx evoked myelin loss and white matter CNS pathology, tremor, hind limb paralysis and BW loss after 30 d. | [33] |
| Oligodendroglia: MOG-Cre; R26-LSL-DTR | 400 ng/mouse (≈16 ng/g) DTx in PBS once daily for seven days i.p. DTx: Merck |
Depletion of OGC-induced axonal injury, but did not cause neuronal cell death | [46] |
| ETS domain factor-positive 5HT neurons in adult mice: Pet1-Cre; R26-LSL-DTR | 5, 50 and 250 ng/g DTx i.p. in saline; 1, 3, 5 times per week for 1, 3 or 6 weeks Cumulative dose of DTx ranged from 2 to 35 µg. DTx: Sigma DO564 |
DTx-evoked reduction of 5-HT neurons (ca. 80%). Nonspecific effectsand increase in mortality at high cumulative dose. Drop of body temperature at 1 week |
[41] |
| 5HT neurons: Pet1-Cre; R26-LSL-DTR | 20 ng/g DTx i.p. 1 × /d for two days DTx: Sigma |
Enhanced dendritic length of newborn hippocampal neurons | [47] |
| Microglia: Tamoxifen-inducible CX3CR-CreERT; R26-LSL-DTR | 2 × 2 mg tamoxifen s.c. at the age of 12–14 days to induce DTR expression in microglia 500 ng DTx i.p. per mouse (≈20 ng/g) once daily for 3 consecutive days at the age of 8 weeks DTx: Merck Millipore |
Ablation of 80% of microglia in the brain and the spinal cord 3 days after DTx injection | [48] |
| Microglia: Tamoxifen-inducible CX3CR-CreERT; R26-LSL-DTR | 1 µg/mouse (≈40 ng/g) i.p. for 3 consecutive days DTx: Sigma | Deficits in multiple learning tasks and reduction in motor learning-dependent synapse formation | [42] |
| Agouti-related protein-positive neurons: AgRP-Cre; R26-LSL-DTR | DTx i.p. in neonates or adult mice | Ablation of NPY/AgRP neurons in adult mice resulted in rapid starvation. | [39] |
| Agouti-related protein-positive neurons: AgRP-Cre; R26-LSL-DTR | 50 ng/g 2 × i.m. 2d apart in 6-week-old mice DTx: List Biological Laboratories | Ablation of AgRP neurons led to increase of cFOS in subsets of neurons and gliosis | [40] |
| Itch sensing neurons: Advillin-Cre; R26-LSL-DTR and subsequently Somatostatin SstCre mice X Advillin-DTR to produce heterozygote Sst-Cre: Avil-Cre-DTR/+ mice | 40 ng/g of DTx, 2 injections, 3 days apart | Reduced scratching behavior evoked by interleukin-31 or agonist at the 5HT1F receptor | [49] |
| Glucose transporter Glut4-Cre; R26-LSL-DTR Pro-opiomelanocortin Pomc-Cre; R26-LSL-DTR |
Stereotaxic hypothalamic injection of 4 ng DTx/mouse (≈0.16 ng/g) | Anorexia in Glut4-DTR mice, hyperphagia in Pomc-DTR mice | [50] |
| Single minded-1-positive hypothalamic neurons: Sim1-Cre; R26-LSL-DTR |
Intra-cerebro-ventricular (ICV) 2.5 ng DTx/mouse in 2 µL artificial CSF (≈0.1 ng/g) | Ablation of Sim1-neurons resulted in obesity | [51] |
| Tyrosine hydroxylase-positive neurons: TH-Cre; R26-LSL-DTR |
Pegylated DTx (Calbiochem) 0.02 pmol/g once daily for 8 consecutive days |
PEGy-DTx led to regional ablation of sympathetic neurons. Pegylation prevented crossing the blood-brain barrier | [43] |
Cre/loxP models were generated by crossing the respective Cre-mouse with a mouse carrying DTR headed with a loxP-STOP-loxP site (LSL-site). The construct was inserted into the Rosa26 locus (R26-LSL-DTR). Cre-recombinase excised the STOP codon, leading to DTR expression in Cre-positive (Cre+) cells.