Knock-in rat lines with Cre recombinase at the dopamine D1 and adenosine 2a receptor loci.

Genetically-modified mice have been widely used in neuroscience. Our understanding of the basal ganglia in particular has been greatly assisted by BAC mutants with selective transgene expression in striatal neurons forming the direct or indirect pathways. However, for more sophisticated behavioral tasks and larger intracranial implants, rats are preferred. Furthermore, BAC lines can show variable expression patterns depending upon genomic insertion site. We therefore used CRISPR-Cas9 gene editing to generate two novel knock-in rat lines, specifically encoding iCre recombinase immediately after the dopamine D1 receptor (Drd1a) or adenosine 2a receptor (Adora2a) loci. We confirmed these rats show selective, functional Cre expression in the direct and indirect pathways respectively, using a combination of in situ hybridization and viral transfections. Finally, we verified normal movement, learning, and motivation across a range of behavioral paradigms. We expect these new D1-Cre and A2a-Cre rat lines to be widely used to study both normal brain functions and neurological and psychiatric pathophysiology.