This invention relates to novel mouse and rat models that permit the temporal death of neuronal precursor cells at any time point. Other existing methods of decreasing neurogenesis are relatively non-specific (e.g., injecting glucocorticoids) or require expensive equipment (e.g., focal x-irradiation)
These mice and rats are being used to inhibit adult neurogenesis in order to study the normal function of adult neurogenesis and to model disease states thought to feature decreased neurogenesis, such as chronic stress, anxiety, and depression.
The murine models have been engineered to express a herpes simplex virus gene called HSV-TK in neuronal precursor cells (through the use of a GFAP promoter). Cells that express HSV-TK undergo programmed death when exposed to a molecule called ganciclovir. The combination of these elements permits stopping neurogenesis at any time point in development by selectively providing ganciclovir to mice or rats expressing HSV-TK in neuronal precursor cells.
- These transgenic animals could be used as models for diseases thought to feature deficits in adult neurogenesis, including depression, anxiety, chronic stress-related illnesses, schizophrenia, drug addiction.
- The animals could be used to determine whether drugs alter behavioral phenotypes by altering neurogenesis or whether they act downstream or independently of neurogenesis.
Mouse and rat models are specific and require minimal equipment