FAT10/diubiquitin-like protein-deficient mice exhibit minimal phenotypic differences.
The FAT10 gene encodes a diubiquitin-like protein containing two tandem head-to-tail ubiquitin-like domains. There is a high degree of similarity between murine and human FAT10 sequences at both the mRNA and protein levels. In various cell lines, FAT10 expression was shown to be induced by gamma interferon or by tumor necrosis factor alpha. In addition, FAT10 expression was found to be up-regulated in some Epstein-Barr virus-infected B-cell lines, in activated dendritic cells, and in several epithelial tumors. However, forced expression of FAT10 in cultured cells was also found to produce apoptotic cell death. Overall, these findings suggest that FAT10 may modulate cellular growth or cellular viability. Here we describe the steps to generate, by genetic targeting, a FAT10 gene knockout mouse model. The FAT10 knockout homozygous mice are viable and fertile. No gross lesions or obvious histological differences were found in these mutated mice. Examination of lymphocyte populations from spleen, thymus, and bone marrow did not reveal any abnormalities. However, flow cytometry analysis demonstrated that the lymphocytes of FAT10 knockout mice were, on average, more prone to spontaneous apoptotic death. Physiologically, these mice demonstrated a high level of sensitivity toward endotoxin challenge. These findings indicate that FAT10 may function as a survival factor.
Canaan
Allon
A
Department of Genetics, The Anlyan Center, Yale University School of Medicine, 300 Cedar St., TAC S-310, New Haven, CT 06510, USA.
Yu
Xiaofeng
X
Booth
Carmen J
CJ
Lian
Jin
J
Lazar
Isaac
I
Gamfi
Serwa L
SL
Castille
Katrina
K
Kohya
Naohiko
N
Nakayama
Yasuhiro
Y
Liu
Yuan-Ching
YC
Eynon
Elizabeth
E
Flavell
Richard
R
Weissman
Sherman M
SM
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology; D003713:Dendritic Cells / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010641:Phenotype; D018805:Sepsis / Q000235:genetics; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology; D014452:Ubiquitins / Q000235:genetics / Q000502:physiology*
C512253:FAT10 protein, mouse; D008070:Lipopolysaccharides; C109184:UBD protein, human; D014452:Ubiquitins