TY - JOUR
T1 - FAT10/diubiquitin-like protein-deficient mice exhibit minimal phenotypic differences
AU - Canaan, Allon
AU - Yu, Xiaofeng
AU - Booth, Carmen J.
AU - Lian, Jin
AU - Lazar, Isaac
AU - Gamfi, Serwa L.
AU - Castille, Katrina
AU - Kohya, Naohiko
AU - Nakayama, Yasuhiro
AU - Liu, Yuan Ching
AU - Eynon, Elizabeth
AU - Flavell, Richard
AU - Weissman, Sherman M.
PY - 2006/7/1
Y1 - 2006/7/1
N2 - 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 marine 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.
AB - 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 marine 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.
UR - http://www.scopus.com/inward/record.url?scp=33745456782&partnerID=8YFLogxK
U2 - 10.1128/MCB.00966-05
DO - 10.1128/MCB.00966-05
M3 - Article
C2 - 16782901
AN - SCOPUS:33745456782
SN - 0270-7306
VL - 26
SP - 5180
EP - 5189
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 13
ER -