Fus deficiency in mice results in defective B-lymphocyte development and activation, high levels of chromosomal instability and perinatal death

The gene FUS (also known as TLS (for translocated in liposarcoma) and hnRNP P-2) is translocated with the gene encoding the transcription factor ERG-1 in human myeloid leukaemias(1-3) Although the functions of wild-type FUS a re unknown, the protein contains an RNA-recognition motif and is a componen t of nuclear riboprotein complexes(4,5). FUS resembles a transcription fact or in that it binds DNA. contributes a transcriptional activation domain to the FUS-ERG oncoprotein and interacts with several transcription factors i n vitro(6-8). TO better understand FUS function in vivo, we examined the co nsequences of disrupting Fus in mice. Our results indicate that Fus is esse ntial for viability of neonatal animals, influences lymphocyte development in a non-cell-intrinsic manner, has an intrinsic role in the proliferative responses of B cells to specific mitogenic stimuli and is required for the maintenance of genomic stability. The involvement of a nuclear riboprotein in these processes in vivo indicates that Fus is important in genome mainte nance.