Parthenogenetically activated oocytes of importin with successful pronuclear formation showed a markedly decreased capability to develop into two-cell embryos. Again no further cleavage could be observed. These results indicate that the Isoforskolin developmental arrest in importin a7-deficient embryos is independent of paternal factors. In order to clarify whether anomalies in pronuclear membrane formation account for the developmental block in importin a7deficient embryos, we performed immunocytochemistry using a specific antibody against nucleoporins. The developmental block of importin a7-deficient embryos coincides with the onset of ZGA. ZGA is an essential step for maternal-to-zygotic-transition and results in a novel gene expression profile which establishes the totipotent state of each blastomer in the cleavage-stage embryo. First endogenous transcription in mice occurs in the late zygote stage and inhibition of RNA polymerase II with a-amanitin results in a block at the two-cell stage. We therefore tested the ability of importin a7-deficient embryos to activate the zygotic genome by performing reverse transcription PCR for several genes that have recently been published to be markers of ZGA. mRNA expression of eukaryotic translation initiation factor 1A, importin a5 and murine endogenous retrovirus-like gene was analysed in oocytes and early embryos of importin a7-deficient and control females. In FALS, mutations in the gene encoding the Cu/Zn superoxide dismutase, a ubiquitously-expressed free-radical defense enzyme, are associated with misfolding of this normally stable homodimeric protein _ENREF_7. Recent studies have also detected misfolded SOD1 in sporadic forms of the disease in which SOD1 mutation is excluded, suggesting that non-native conformers of SOD1 may participate in a common pathological mechanism shared by all types of ALS. In Brusatol addition to SOD1, heritable mutation of two other genes are implicated in FALS, and associated with protein mislocalization and aggregation: the RNA-processing proteins fused in sarcoma, originally named translocated in liposarcoma, and TARDNA binding protein.