Targeted disruption of fad24, a regulator of adipogenesis,causes pre-implantation embryonic lethality due to the growth defect at the blastocyst stage |
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Authors: | Natsuki Ochiai Makoto Nishizuka Tomomi Miyamoto Ichiro Miyoshi Masahito Ikawa Shigehiro Osada Masayoshi Imagawa |
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Affiliation: | 1. Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan;2. Department of Comparative and Experimental Medicine and Center for Experimental Animal Science, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan;3. Genome Information Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan |
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Abstract: | In previous studies, we identified a novel gene, factor for adipocyte differentiation 24 (fad24), which plays an important role during the early stages of adipogenesis in mouse 3T3-L1 cells. Moreover, overexpression of fad24 increased the number of smaller adipocytes in white adipose tissue and improved glucose metabolic activity in mice, thus indicating that fad24 functions as a regulator of adipogenesis in vivo. However, the physiological roles of fad24 in vivo are largely unknown. In this study, we attempted to generate fad24-deficient mice by gene targeting. No fad24-null mutants were recovered after embryonic day 9.5 (E9.5). Although fad24-null embryos were detected in an expected Mendelian ratio of genotypes at E3.5, none of the homozygous mutants developed into blastocysts. In vitro culture experiments revealed that fad24-null embryos develop normally to the morula stage but acquire growth defects during subsequent stages. The number of nuclei decreased in fad24-deficient morulae compared with that in wild-type ones. These results strongly suggested that fad24 is essential for pre-implantation in embryonic development, particularly for the progression to the blastocyst stage. |
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Keywords: | DAPI, 4&prime ,6-diamidino-2-phenylindole E, embryonic day fad, factor for adipocyte differentiation HBO1, histone acetyltransferase binding to ORC1 IVF, in vitro fertilization Neo, neomycin resistance Noc, nucleolar complex-associated protein PBS, phosphate buffered saline PCR, polymerase chain reaction TK, thymidine kinase |
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