Neuron-specific genome modification in the adult rat brain using CRISPR-Cas9

2019

Challenge

Rat models of addiction and other neurological disorders have behavioral advantages over mice; however, the development of genetically modified rats has been very slow compared to mice. 

Advance

IRP researchers led by senior investigator Brandon Harvey, Ph.D., created a set of novel genetically modified rats along with a collection of viruses that could be used to change the DNA in the neurons within their brains. The technology utilizes a CRISPR-Cas9 system to inactivate genes in specific populations of neurons with precise timing and is also adaptable to other cell types and tissues in the adult rat brain.

Impact

These tools will enable future research into how certain genes influence the function of specific neuronal circuits governing physical movement and complex cognitive behaviors in the adult rat brain. Using these new techniques to create new animal models will expand our understanding of the relationship between specific genes and the development of substance abuse or neurological disorders such as Parkinson’s disease.

Publications

Bäck S, Necarsulmer J, Whitaker LR, Coke LM1, Koivula P, Heathward EJ, Fortuno LV, Zhang Y, Yeh CG, Baldwin HA, Spencer MD, Mejias-Aponte CA, Pickel J, Hoffman AF, Spivak CE, Lupica CR, Underhill SM, Amara SG, Domanskyi A, Anttila JE, Airavaara M, Hope BT, Hamra FK, Richie CT, Harvey BK. (2019). Neuron-Specific Genome Modification in the Adult Rat Brain Using CRISPR-Cas9 Transgenic Rats. Neuron. Apr 3;102(1):105-119.e8.