Pendeville H, Carpino N, Marine J C, Takahashi Y, Muller M, Martial J A, Cleveland J L
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Mol Cell Biol. 2001 Oct;21(19):6549-58. doi: 10.1128/MCB.21.19.6549-6558.2001.
Overexpression and inhibitor studies have suggested that the c-Myc target gene for ornithine decarboxylase (ODC), the enzyme which converts ornithine to putrescine, plays an important role in diverse biological processes, including cell growth, differentiation, transformation, and apoptosis. To explore the physiological function of ODC in mammalian development, we generated mice harboring a disrupted ODC gene. ODC-heterozygous mice were viable, normal, and fertile. Although zygotic ODC is expressed throughout the embryo prior to implantation, loss of ODC did not block normal development to the blastocyst stage. Embryonic day E3.5 ODC-deficient embryos were capable of uterine implantation and induced maternal decidualization yet failed to develop substantially thereafter. Surprisingly, analysis of ODC-deficient blastocysts suggests that loss of ODC does not affect cell growth per se but rather is required for survival of the pluripotent cells of the inner cell mass. Therefore, ODC plays an essential role in murine development, and proper homeostasis of polyamine pools appears to be required for cell survival prior to gastrulation.
过表达和抑制剂研究表明,作为将鸟氨酸转化为腐胺的酶,鸟氨酸脱羧酶(ODC)的c-Myc靶基因在多种生物学过程中发挥重要作用,包括细胞生长、分化、转化和凋亡。为了探究ODC在哺乳动物发育中的生理功能,我们培育了ODC基因被破坏的小鼠。ODC杂合子小鼠存活、正常且可育。尽管合子型ODC在植入前的整个胚胎中都有表达,但ODC的缺失并未阻止胚胎正常发育到囊胚阶段。胚胎第3.5天的ODC缺陷胚胎能够在子宫内着床并诱导母体蜕膜化,但此后基本无法进一步发育。令人惊讶的是,对ODC缺陷囊胚的分析表明,ODC的缺失本身并不影响细胞生长,而是内细胞团多能细胞存活所必需的。因此,ODC在小鼠发育中起重要作用,并且在原肠胚形成之前,多胺池的适当稳态似乎是细胞存活所必需的。