TY - JOUR T1 - Knock-in rat lines with Cre recombinase at the dopamine D1 and adenosine 2a receptor loci JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0163-19.2019 SP - ENEURO.0163-19.2019 AU - Jeffrey R. Pettibone AU - Jai Y. Yu AU - Rifka C. Derman AU - Thomas W. Faust AU - Elizabeth D. Hughes AU - Wanda E. Filipiak AU - Thomas L. Saunders AU - Carrie R. Ferrario AU - Joshua D. Berke Y1 - 2019/08/26 UR - http://www.eneuro.org/content/early/2019/08/26/ENEURO.0163-19.2019.abstract N2 - Genetically-modified mice have become standard tools in neuroscience research. 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, rat models are preferred. Furthermore, BAC lines can show variable expression patterns depending upon genomic insertion site. We therefore used CRISPR/Cas9 to generate two novel knock-in rat lines specifically encoding Cre recombinase immediately after the dopamine D1 receptor (Drd1a) or adenosine 2a receptor (Adora2a) loci. Here we validate these lines using in situ hybridization and viral vector mediated transfection to demonstrate selective, functional Cre expression in the striatal direct and indirect pathways respectively. We used whole-genome sequencing to confirm the lack of off-target effects, and established that both rat lines have normal locomotor activity and learning in simple instrumental and Pavlovian tasks. We expect these new D1-Cre and A2a-Cre rat lines will be widely used to study both normal brain functions and neurological and psychiatric pathophysiology.SIGNIFICANCE STATEMENT This work presents the generation and validation of two novel knock-in rat lines, We demonstrate that the Cre transgene was correctly inserted at the intended genomic locations only, and that the rats show normal behavior in a range of simple tests. We validate that Cre is expressed with high specificity and consistency, and produces functional Cre-dependent protein expression in vivo. Among other applications, these lines will be valuable tools for selective investigations of the striatal direct and indirect pathways. ER -