Search

We present genetic and molecular data demonstrating linkage of the gene for steroid sulfatase (Sts) to the mutation sex reversed (Sxr) definitively showing the existance of a functional allele for Sts mapping to the pseudoautosomal region of the mouse Y chromosome. Thus, in mouse, functional Sts genes are present in the pseudoautosomal region of both the X and Y chromosomes. This is in contrast to man where Sts has been mapped to the short arm of the X just centromeric to the pseudoautosomal region. Only a single recombinant separating Sts and Sxr was found out of 103 male meioses analyzed; double recombinants were not found between sex (Tdy), Sts and Sxr. If the rate of recombination in the pseudoautosomal region in male mice is equivalent to that in man and thus 7-10X higher than normal, then our data suggest that the distance between Sts and Sxr (or the telomere of the Y) is approximately 100-200 kb in length. Our data is in contrast to a recent report of a recombination frequency separating Sts and Sxr of as high as 6.2-9.8%.

Male and female gamete nuclei are required to ensure the full-term development of the mouse embryo. Differential expression of the two genomes has been proposed as the basis for this requirement. In order to investigate whether some interactions between the paternal and the maternal genomes are essential before or at the time of the activation of the embryonic genome, we have constructed diploid embryos from haploid parthenotes and androgenotes at the late 2-cell stage. These embryos developed to term into normal offsprings. This shows that the male and the female genomes can be activated separately and are still able to ensure complete development when put together in cytoplasm synchronized with the nuclei. These experiments also show that the egg cytoplasm does not need any male contribution before the late 2-cell stage.

Recent experiments using nuclear transfer between mouse embryos shows that the parental genomes are not equivalent: both of them must be present at least in a part of the blastomeres to allow full term development of the embryo. The paternal genome is preferentially involved in the development of trophoectodermic cells and appears to be eliminated from the primitive ectoderm when kept alone in androgenetic cells aggregated with normal ones. Differences of expression between parental genomes affect not only the X chromosome, but also several autosomes as evidenced by genetic analysis using meiotic non-disjunction. The nature of the imprinting mechanism that leads to the modification of parental homologous chromosomes is unknown. From experiments involving a particular strain of mice called DDK it appears that the egg cytoplasm may exert a specific action not only on the male pronucleus at the one-cell stage, but also on the paternal contribution of the diploid nucleus of the embryo at the 2-cell stage; a paternal developmental effect on the cytoplasm of one-cell stage embryo can also be demonstrated. These results show that nucleocytoplasmic interactions regulate early paternal gene expression differently from the maternal one.

The effect of c-myc gene expression on F9 teratocarcinoma stem cell differentiation was studied by transfecting mouse metallothionein I promoter-driven human c-myc genes into F9 cells. Human c-myc gene expression was triggered by cadmium treatment at different stages of differentiation. When this expression was induced before or just after addition of retinoic acid plus cyclic AMP (RA +cAMP), the death of 70-80% of the cells was observed. This cell mortality was not observed either when the parental F9 cells were induced to differentiate in the presence of cadmium or when the undifferentiated transfected clone was permanently grown in the presence of this inducer. The 30% surviving cells underwent terminal differentiation despite high c-myc mRNA levels and expressed differentiation-specific genes normally like their parental F9 cells. When cadmium was added 24 or 48 hr after RA +cAMP, no cell mortality or any other detectable effect on differentiation were observed, even though c-myc gene transcripts were induced. We therefore conclude that c-myc gene expression only inhibits F9 differentiation at an early stage in 70-80% of cells. The significance of these results will be discussed.

The ability of ruthenium red to induce chromosome aberrations in vivo in mammalian somatic cells has been evaluated by the micronucleus test on mouse bone marrow cells. Our results show that this compound, when administered i.p. at a sublethal level, can be considered as a weak clastogen.