The Moloney murine sarcoma virus (MSV) is a representative of a class of replication-defective
retroviruses that transform fibroblasts in culture and induce sarcomas in vivo. It arose by
recombination between the Moloney murine leukemia virus and a sequence derived from mouse
cells. The mouse cell-derived segment of MSV, termed v-mos, is required for the induction and
maintenance of viral transformation. The normal mouse analog of v-mos has been molecularly
cloned. The c-mos proto-oncogene encodes a 37-39K cytoplasmic serine/threonine kinase
implicated in the meiotic maturation events during murine spermatogenesis and
oogenesis. In Xenopus, ectopic expression of pp39mos can promote both the
meiotic maturation of oocytes and also arrest the cleavage of blastomeres.
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.
General function
Cell death/survival, Cell cycle regulation
Comment
Mos limits the number of meiotic divisions in urochordate eggs. Dumollard R et al. Mos kinase is a universal mediator of oocyte meiotic maturation and is produced during oogenesis and destroyed after fertilization. The hallmark of maternal meiosis is that two successive M phases (meiosis I and II) drive two rounds of asymmetric cell division (ACD). However, how the egg limits the number of meioses to just two, thereby preventing gross aneuploidy, is poorly characterized. Here, in urochordate eggs, we show that loss of Mos/MAPK activity is necessary to prevent entry into meiosis III. Remarkably, maintaining the Mos/MAPK pathway active after fertilization at near physiological levels induces additional rounds of meiotic M phase (meiosis III, IV and V). During these additional rounds of meiosis, the spindle is positioned asymmetrically resulting in further rounds of ACD. In addition, inhibiting meiotic exit with Mos prevents pronuclear formation, cyclin A accumulation and maintains sperm-triggered Ca(2+) oscillations, all of which are hallmarks of the meiotic cell cycle in ascidians. It will be interesting to determine whether Mos availability in mammals can also control the number of meioses as it does in the urochordates. Our results demonstrate the power of urochordate eggs as a model to dissect the egg-to-embryo transition.
Cellular localization
Cytoplasmic
Comment
Ovarian function
Oogenesis, Oocyte maturation
Comment
This gene is upregulated during oocyte maturation (Fig. 2) Wang et al 2004 .
Expression regulated by
Comment
Translational Regulation of MOS mRNA in Pig Oocytes Dai Y, et al .
The temporal and spatial translation control of stored mRNA in oocytes is regulated by elements in their 3' untranslated region (3'UTR). The MOS 3' UTR in pig oocytes is both heterogeneous (180, 480 or 530nt), contains multiple U-rich elements and extensive A-rich sequences (CA13CA5CA5CA6). We have examined the role of these potential regulatory elements by fusing wild type or mutant MOS 3'UTRs to luciferase mRNA and then injecting these chimaeric transcripts into oocytes. We draw six main conclusions from this study. First, the length of the MOS 3'UTR tightly controls the level of translation of luciferase during oocyte maturation. Second, two U-rich (U5A) elements and the hexanucleotide signal (AAUAAA) are required for translation. Third, mutations, duplications or relocations of the A-rich sequence reduce or block translation. Fourth, the relative importance of the A-rich and U-rich elements in controlling the level of translation differs. Fifth, none of our MOS 3'UTR manipulations relieved translational repression before germinal vesicle breakdown. Sixth, all the MOS mRNA variants underwent polyadenylation during maturation. While mutations to the hexanucleotide signal block both polyadenylation and translation, mutations to either the A-rich sequence or to the U-rich elements block translation but without fully blocking polyadenylation. We conclude that MOS mRNA translation in pig oocytes is subject to a more extensive series of controls than that in lower vertebrates.
Ovarian localization
Oocyte
Comment
Translational Regulation of MOS Messenger RNA in Pig Oocytes Dai Y, et al .
The temporal and spatial translation control of stored mRNA in oocytes is regulated by elements in their 3'-untranslated region (3'-UTR). The MOS 3'-UTR in pig oocytes is both heterogeneous (180, 480, or 530 nucleotides), and it contains multiple U-rich elements and extensive A-rich sequences (CA(13)CA(5)CA(5)CA(6)). We have examined the role of these potential regulatory elements by fusing wild-type or mutant MOS 3'-UTRs to luciferase mRNA and then injecting these chimeric transcripts into oocytes. We draw six main conclusions. First, the length of the MOS 3'-UTR tightly controls the level of translation of luciferase during oocyte maturation. Second, two U-rich (U(5)A) elements and the hexanucleotide signal (AAUAAA) are required for translation. Third, mutations, duplications, or relocations of the A-rich sequence reduce or block translation. Fourth, the relative importance of the A-rich and U-rich elements in controlling the level of translation differs. Fifth, none of our MOS 3'-UTR manipulations relieved translational repression before germinal vesicle breakdown. Sixth, all the MOS mRNA variants underwent polyadenylation during maturation. Whereas mutations to the hexanucleotide signal block both polyadenylation and translation, mutations to either the A-rich sequence or the U-rich elements block translation without fully blocking polyadenylation. We conclude that MOS mRNA translation in pig oocytes is subject to a more extensive series of controls than that in lower vertebrates.
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment:Colledge WH et al 1994 reported that disruption of c-mos causes parthenogenetic development of unfertilized mouse eggs.
To
elucidate the role of pp39mos the authors have generated homozygous mutant mice by
gene targeting in embryonic stem cells. These mice are viable and mutant males
are fertile, demonstrating that pp39mos is not essential for spermatogenesis. In
contrast, mutant females, have a reduced fertility because of the failure of mature
eggs to arrest during meiosis. c-mos-/- oocytes undergo germinal vesicle
breakdown and extrusion of both polar bodies followed in some cases by
progression into cleavage. Mutant females also develop ovarian cysts. These
results demonstrate that a major role for pp39mos is to prevent the spontaneous
parthenogenetic activation of unfertilized eggs.
Hashimoto N et al 1994 reported parthenogenetic activation of oocytes in c-mos-deficient mice.
They 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.