Dffb-KO Mouse

DFFB, also known as DNA fragmentation factor subunit beta, plays a crucial role in the intracellular generation of cell-free DNA (cfDNA) [1,2,3]. cfDNA is a significant non-invasive biomarker for cancer and prenatal testing. DFFB, along with intracellular DNASE1L3 and other nucleases, initiates the fragmentation process of cfDNA within cells [1]. This process is vital as the balance of cfDNA generation and clearance is essential for maintaining health and preventing diseases such as cancer and systemic lupus erythematosus (SLE) [2].

In nuclease-deficient mouse models, analysis of cfDNA fragment ends showed that DFFB has a specific cutting preference, revealing its role in the stepwise process of cfDNA fragmentation [1]. The proportion of long cell-free DNA molecules originating from transcription start sites is lower in Dffb-deficient mice compared to wild-type mice, indicating DFFB's influence on the genomic origin of cfDNA [4]. Also, the deletion of Dffb in mouse models led to certain aberration in the profile of plasma DNA jagged ends, though less significant compared to Dnase1l3 deletion, which is related to SLE [5].

In summary, DFFB is essential for the intracellular stage of cfDNA fragmentation. Mouse models with Dffb deficiency have provided insights into its role in cfDNA-related biological processes and its potential connection to diseases like SLE. Understanding DFFB's function helps in elucidating the biology of cfDNA and may contribute to the development of new diagnostic and therapeutic strategies for associated diseases.