Pdcd1-flox Mouse

Pdcd1, encoding PD-1, is an important gene as PD-1 is a key immune checkpoint protein and a major immunotherapy target for treating cancer [1,2]. It is involved in immune-related pathways, and its dysregulation can lead to abnormal immune responses. Alternative splicing of Pdcd1 generates an exon 3-skipped isoform PD-1Δ3, which is suggested to have an antagonistic role to PD-1 [1].

The mechanism underlying Pdcd1 exon 3 splicing has been explored. Through a minigene system, exon 3 skipping was confirmed as the main alternative splicing event. Two splicing enhancers (ESE3a and ESE3b) in exon 3 were mapped by deletion analysis. MATR3 was defined as a splicing activator during Pdcd1 exon 3 splicing through binding to ESE3b, and its activity is counteracted by an RNA secondary structure around ESE3b and an RNA helicase DDX5. ASOs that efficiently promote Pdcd1 exon 3 skipping in both minigene and endogenous-gene contexts were also identified [1].

In conclusion, Pdcd1 is crucial in cancer immunotherapy due to its role in encoding the key immune checkpoint protein PD-1. Understanding the splicing mechanism of Pdcd1 provides insights into potential drug development, as the identified ASOs may be further studied as potential drug candidates for cancer treatment [1].