Within the large family of non-coding RNAs there is a newly characterized class called circular RNAs (circRNAs). These transcripts mostly derive from exonic sequences and are the products of an alternative mechanism of splicing known as backsplicing. These products are single-stranded RNA molecules with covalently joined ends. Due to the high expression of numerous circular transcripts in nerve tissue samples, we have selected a circRNA derived from the Tulp4 gene to perform a functional characterization. To do so, we have generated a transgenic knock-out mouse line to model circTulp4 loss-of-function in vivo. CircTulp4-KO mice are viable and fertile but have alterations in excitatory neurotransmission.
More recently, we performed a neuronal morphological characterization through a microscopic quantitative analysis of brain sections from a Thy1-eGFP mouse line, where a sparse population of neurons express EGFP. We observed that circTulp4-KO mice do not differ in the complexity and total length of the dendritic arbor. However, we observed that KO mice have a higher dendritic spine density and a marginal increase in spine volume.
Furthermore, we made an extensive behavioral characterization of this mouse line. We found that circTulp4 loss-of-function led to hyperlocomotion under illuminated (stressful) conditions, increased startle response and an altered stress-responsivity. Together, these results suggest that circTulp-KO mice display an increased anxiety-related behavior.