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Comment |
SOX2 Modulates Reprogramming of Gene Expression in Two-Cell Mouse Embryos. Pan H et al. Sox2 is a key gene that controls transcriptional networks required for pluripotency. The role of Sox2 in the developmental transition of a highly differentiated oocyte to totipotent blastomeres of the early preimplantation, however, is not known. We report that Sox2, which is localized in the nucleus, is first zygotically expressed during the 2-cell stage and that its expression dramatically increases between the morula and blastocyst stages. Injecting a cRNA encoding Sox2 into 1-cell embryos resulted in over-expression of SOX2 by ~70% and developmental arrest at the 2-cell stage, whereas injecting cRNAs encoding Pou5f1, Myc (also known as c-Myc) or Klf4 has little effect on the ability of 2-cell embryos to cleave to the 4-cell stage. Global transcription assessed by BrUTP incorporation is reduced by ~15%, and transcript profiling revealed that ~15% of zygotically-expressed genes are dramatically repressed in 2-cell embryos over-expressing SOX2. Furthermore, over-expressing a dominant-negative SOX2 perturbs reprogramming of gene expression in 2-cell embryos, but to a much lesser extent than observed following over-expression of SOX2, and also led to developmental failure prior to 8-cell stage but after the 2-cell stage. Results of these experiments implicate Sox2 as a critical transcriptional regulator in oocyte-to-embryo transition that entails formation of totipotent blastomeres and that the amount of Sox2 is critical for successful execution of this transition.
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Mutations |
2 mutations
Species: mouse
Mutation name: None
type: null mutation
fertility: infertile - ovarian defect
Comment: Essential role of sox2 for the establishment and maintenance of the germ cell line. Campolo F et al. Sox2 is a pluripotency-conferring gene expressed in primordial germ cells (PGCs) and postnatal oocytes, but the role it plays during germ cell development and early embryogenesis is unknown. Since Sox2 ablation causes early embryonic lethality shortly after blastocyst implantation, we generated mice bearing Sox2-conditional deletion in germ cells at different stages of their development through the Cre/loxP recombination system. Embryos lacking Sox2 in PGCs show a dramatic decrease of germ cell numbers at the time of their specification. At later stages, we found that Sox2 is strictly required for PGC proliferation. On the contrary Sox2 deletion in meiotic oocytes does not impair postnatal oogenesis and early embryogenesis, indicating that it is not essential for oocyte maturation nor for zygotic development. We also show that Sox2 regulates Kit expression in PGCs and binds to discrete transcriptional regulatory sequences of this gene, which is known to be important for PGCs survival and proliferation. Sox2 also stimulates the expression of Zfp148 which is required for normal development of fetal germ cells, and Rif1, a potential regulator of PGC pluripotency.
Species: mouse
Mutation name: None
type: null mutation
fertility: subfertile
Comment: Production of Sry knockout mouse using TALEN via oocyte injection. Kato T 2013 et al.
Recently developed transcription activator-like effector nuclease (TALEN) technology has enabled the creation of knockout mice, even for genes on the Y chromosome. In this study, we generated a knockout mouse for Sry, a sex-determining gene on the Y chromosome, using microinjection of TALEN RNA into pronuclear stage oocytes. As expected, the knockout mouse had female external and internal genitalia, a female level of blood testosterone and a female sexually dimorphic nucleus in the brain. The knockout mouse exhibited an estrous cycle and performed copulatory behavior as females, although it was infertile or had reduced fertility. A histological analysis showed that the ovary of the knockout mouse displayed a reduced number of oocytes and luteinized unruptured follicles, implying that a reduced number of ovulated oocytes is a possible reason for infertility and/or reduced fertility in the KO mouse.
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