Abstract：
:Historically, the rat has been the preferred animal model for behavioral studies. Limitations in genome modification have, however, caused a lag in their use compared to the bevy of available transgenic mice. Here, we have developed several transgenic tools, including viral vectors and transgenic rats, for targeted genome modification in specific adult rat neurons using CRISPR-Cas9 technology. Starting from wild-type rats, knockout of tyrosine hydroxylase was achieved with adeno-associated viral (AAV) vectors expressing Cas9 or guide RNAs (gRNAs). We subsequently created an AAV vector for Cre-dependent gRNA expression as well as three new transgenic rat lines to specifically target CRISPR-Cas9 components to dopaminergic neurons. One rat represents the first knockin rat model made by germline gene targeting in spermatogonial stem cells. The rats described herein serve as a versatile platform for making cell-specific and sequence-specific genome modifications in the adult brain and potentially other Cre-expressing tissues of the rat.
journal_name
Neuronjournal_title
Neuronauthors
Bäck S,Necarsulmer J,Whitaker LR,Coke LM,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,doi
10.1016/j.neuron.2019.01.035subject
Has Abstractpub_date
2019-04-03 00:00:00pages
105-119.e8issue
1eissn
0896-6273issn
1097-4199pii
S0896-6273(19)30062-5journal_volume
102pub_type
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