Nishizuka Makoto, Kishimoto Keishi, Kato Ayumi, Ikawa Masahito, Okabe Masaru, Sato Ryuichiro, Niida Hiroyuki, Nakanishi Makoto, Osada Shigehiro, Imagawa Masayoshi
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
Exp Cell Res. 2009 Mar 10;315(5):809-19. doi: 10.1016/j.yexcr.2008.12.013. Epub 2008 Dec 29.
The molecular mechanisms at the beginning of adipogenesis remain unknown. Previously, we identified a novel gene, fad104 (factor for adipocyte differentiation 104), transiently expressed at the early stage of adipocyte differentiation. Since the knockdown of the expression of fad104 dramatically repressed adipogenesis, it is clear that fad104 plays important roles in adipocyte differentiation. However, the physiological roles of fad104 are still unknown. In this study, we generated fad104-deficient mice by gene targeting. Although the mice were born in the expected Mendelian ratios, all died within 1 day of birth, suggesting fad104 to be crucial for survival after birth. Furthermore, analyses of mouse embryonic fibroblasts (MEFs) prepared from fad104-deficient mice provided new insights into the functions of fad104. Disruption of fad104 inhibited adipocyte differentiation and cell proliferation. In addition, cell adhesion and wound healing assays using fad104-deficient MEFs revealed that loss of fad104 expression caused a reduction in stress fiber formation, and notably delayed cell adhesion, spreading and migration. These results indicate that fad104 is essential for the survival of newborns just after birth and important for cell proliferation, adhesion, spreading and migration.
脂肪生成起始阶段的分子机制尚不清楚。此前，我们鉴定出一个新基因，fad104（脂肪细胞分化因子104），它在脂肪细胞分化早期短暂表达。由于敲低fad104的表达会显著抑制脂肪生成，显然fad104在脂肪细胞分化中发挥重要作用。然而，fad104的生理作用仍然未知。在本研究中，我们通过基因靶向技术构建了fad104基因缺失小鼠。尽管这些小鼠以预期的孟德尔比例出生，但均在出生后1天内死亡，这表明fad104对出生后的存活至关重要。此外，对从fad104基因缺失小鼠制备的小鼠胚胎成纤维细胞（MEFs）的分析为fad104的功能提供了新的见解。fad104的缺失抑制了脂肪细胞分化和细胞增殖。此外，使用fad104基因缺失的MEFs进行的细胞黏附和伤口愈合实验表明，fad104表达的缺失导致应力纤维形成减少，并且显著延迟了细胞黏附、铺展和迁移。这些结果表明，fad104对新生儿出生后的存活至关重要，并且对细胞增殖、黏附、铺展和迁移也很重要。
