Recql5-Deficient Mice as a Model for Studying Chromoanagenesis Phenomena

Complex chromosomal rearrangements (CCRs) present significant challenges and opportunities in cancer and congenital disease research. Reproducing these rearrangements experimentally in animal models has been challenging, limiting our insights into their mechanisms and impacts. Recql5 is a critical DNA helicase that participates in replication, transcription, and repair processes. We recently succeeded in facilitating CRISPR/Cas9-mediated induction of CCRs in mice, harboring Recql5 deletion. Some CCRs were accomplished by DNA repair mechanisms, including fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR), characteristics reminiscent of chromoanasynthesis. This phenomenon is a part of chromoanagenesis, which includes other catastrophic chromosomal rearrangements. This chapter discusses the creation of CCR animal models, offering a new perspective for exploring the pathogenesis of chromosomal rearrangements. Recql5-mutant mice will prove to be a valuable tool for further genetic studies, potentially advancing our understanding of disease mechanisms and suggesting directions for future research.