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 P2) is translocated with the gene encoding the transcription factor ERG-1 in human myeloid leukaemias. Although the functions of wild-type FUS are unknown, the protein contains an RNA-recognition motif and is a component of nuclear riboprotein complexes. FUS resembles a transcription factor in that it binds DNA, contributes a transcriptional activation domain to the FUS-ERG oncoprotein and interacts with several transcription factors in vitro. To better understand FUS function in vivo, we examined the consequences of disrupting Fus in mice. Our results indicate that Fus is essential 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 maintenance.
Hicks
G G
GG
Manitoba Institute of Cell Biology and the University of Manitoba, Winnipeg, Canada. hicksgg@cc.umanitoba.ca
Singh
N
N
Nashabi
A
A
Mai
S
S
Bozek
G
G
Klewes
L
L
Arapovic
D
D
White
E K
EK
Koury
M J
MJ
Oltz
E M
EM
Van Kaer
L
L
Ruley
H E
HE
D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D002678:Chimera; D003433:Crosses, Genetic; D005260:Female; D005838:Genotype; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins / Q000378:metabolism; D015183:Restriction Mapping; D012261:Ribonucleoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology
D034441:Heterogeneous-Nuclear Ribonucleoproteins; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins