In Xenopus the c-mos proto-oncogene product (Mos) is essential for the initiation of oocyte maturation, for the progression from meiosis I to meiosis II and for the second meiotic metaphase arrest, acting as an essential component of the cytostatic factor CSF. Its function in mouse oocytes is unclear, however, as is the biological significance of c-mos mRNA expression in testes and several somatic tissues. We have generated c-mos-deficient mice by gene targeting in embryonic stem cells. These mice grew at the same rate as their wild-type counterparts and reproduction was normal in the males, but the fertility of the females was very low. The c-mos-deficient female mice developed ovarian teratomas at a high frequency. Oocytes from these females matured to the second meiotic metaphase both in vivo and in vitro, but were activated without fertilization. The results indicate that in mice Mos plays a role in the second meiotic metaphase arrest, but does not seem to be essential for the initiation of oocyte maturation, spermatogenesis or somatic cell cycle.

A group of retroviruses carrying truncated viral genes has recently been suggested as the cause of new patterns of diseases. One such virus is the replication defective component of the Friend murine leukemia virus (F‐MuLV) complex, called Friend spleen focus forming virus (F‐SFFV). This virus induces erythroblastosis, and a virion envelope‐related glycoprotein, gp55, encoded by F‐SFFV has been suggested as the pathogenic gene. The role of the gp55 gene is, however, yet unclear in the apparently multistep erythroleukemogenesis. By separately producing transgenic mice harboring the whole F‐SFFV DNA, the gp55 gene alone under the control of the retroviral long terminal repeat (LTR) and the gp55 gene under the control of cytoplasmic beta actin transcriptional regulatory unit, we show here that the gp55 gene is capable of inducing neoplastic proliferation of erythroid progenitor cells specifically in the absence of helper virus and other F‐SFFV sequences. Under the control of the viral LTR the gp55 expression was detected only in leukemic tissues, but under the control of cytoplasmic beta‐actin regulatory sequences, the gp55 was also expressed in a variety of normal tissues including preleukemic normal spleens. The development of erythroleukemia was suppressed under the genetic background of C57B1/6 mouse (resistant to F‐MuLV; Fv‐2rr), and required additional events even under the background of DDD mouse (susceptible to F‐MuLV; Fv‐2ss). The p53 and Spi‐1 genes were frequently aberrant in transplanted tumors and cell lines derived from them, but were not in primary leukemic spleens.

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Genes upregulated by p53 were screened using an erythroleukemic cell line (1-2-3) that expresses only the temperature-sensitive p53 by the mRNA differential display method. One of the upregulated genes was identified as the elongation factor-1α (EF-1α) gene, an essential component of the eukaryotic translation apparatus. Three p53-responsive elements were found in the mouse EF-1α gene and in the corresponding human, rat, and frog genes. These elements conferred the capacity for induction by p53. EF-1α is also a microtubule-severing protein. Upon the temperature-shift, the cells developed the morphology and the localization of α-tubulin similar to those of the cells treated with vincristine, a drug that affects microtubules. The microtubule-severing associated with upregulation of EF-1α by p53 may be a cause of the cell death.