V-019
Understanding circTulp4's Involvement in Dopaminergic Activity and Stress-Related Behaviors
Camila Pannunzio1, Lucía Szychowski1, Sebastián Giusti1, Damián Refojo1,2
  1. Biomedicine Research Institute of Buenos Aires - CONICET - Partner Institute of the Max Planck Society - Buenos Aires, Argentina
  2. Max Planck Institute of Psychiatry - Munich, Germany
Presenting Author:
Camila Pannunzio
camilapannunzio4@gmail.com
Circular RNAs (circRNAs) are well-established non-coding RNAs that have recently been recognized for their remarkable diversity and abundance. Although thousands of circRNAs have been discovered, their biological roles remain largely unexplored, partly due to difficulties in generating effective loss-of-function animal models. Previously, our lab identified numerous circRNAs and linear isoforms in human and mouse brain using RNA-seq. Many circRNAs were more highly expressed than linear isoforms in nervous tissue. To investigate the function of a highly abundant circRNA derived from the Tulp4 gene, which is enriched in brain and synaptic compartments, we generated a transgenic knockout mouse line (Tulp4CD) using CRISPR/Cas9. We mutated the splice acceptor site responsible for circTulp4 biogenesis, preserving linear mRNA and protein. Our findings show that circTulp4 modulates excitatory neurotransmission and behavioral sensitivity to aversive stimuli, shown as hyperlocomotion. Here, we show that Tulp4CD mice exhibited enhanced locomotor response to amphetamine, suggesting effects on dopaminergic circuits. RT-qPCR revealed increased DRD2 transcripts in the amygdala and VMAT2 in the hippocampus. Behavioral tests indicated that Tulp4CD mice are more sensitive to stressful stimuli, as evidenced by stronger avoidance in the passive avoidance test. We are extending phenotypic analyses, studying interactors, and exploring circTulp4 in the dopaminergic function.