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The Ets family of transcription factors has been implicated in the etiology of several types of cancer. We cloned and characterized the gene encoding the murine homologue of one Ets family member, Elf-1 (mElf-1), in order to gain insight into its cellular physiology. We examined mElf-1 mRNA expression in normal mouse tissues and in several murine and human cell lines. Expression of mElf-1, although highest in lymphocytes, was observed in a number of hematopoietic cell lineages, including the myeloid, macrophages and erythroid lineages, and was lowest in the murine fibroblast cell line, NIH3T3. Analysis of human and fetal tissue mRNAs confirmed that mElf-1 is expressed in a variety of cell lineages, principally in hematopoietic cells. Western blot analysis using antiserum generated to a synthetic C-terminal peptide of mElf-1, and extracts prepared from cell lines that expressed the mElf-1 mRNA identified multiple mElf-1 species that migrated near the 97-kDa molecular weight marker. Site selection analysis indicated that the binding site preferred by mElf-1 is very similar to that of the Drosophila melanogaster homologue, E74, and to that of Fli-1, another Ets family member. We conclude that the expression of mElf-1 is not restricted to the lymphoid lineage, and suggest that Elf-1 may regulate the transcription of a broad spectrum of genes.

The t(8;21) is associated with 12 – 15% of acute myelogenous leukemias of the M2 subtype. The translocation results in the fusion of two genes, AML1 (CBFA2) on chromosome 21 and ETO (MTG8) on chromosome 8. AML1 encodes a DNA binding factor; the ETO protein product is less well characterized, but is thought to be a transcription factor. Here we describe the isolation and characterization of ETO-2, a murine cDNA that encodes a new member of the ETO family of proteins. ETO-2 is 75% identical to murine ETO and shares very high sequence identities over four regions of the protein with ETO (domain I – III and zinc-finger). Northern analysis identifies ETO-2 transcripts in many of the murine tissues analysed and in the developing mouse embryo. ETO-2 is also expressed in myeloid and erythroid cell lines. We confirmed the nuclear localization of ETO-2 and demonstrated that domain III and the zinc-finger region are not required for nuclear localization. We further showed that a region within ETO, containing domain II, mediates dimerization among family members. This region is conserved in the oncoprotein AML-1/ETO. The recent identification of another ETO-like protein, myeloid translocation gene-related protein 1, together with the data presented here, demonstrates that at least three ETO proteins exist with the potential to form dimers in the cell nucleus.

We used a sensitive silver degeneration staining method to study the effects of insertion of microdialysis probes in rat dorsal hippocampus and neocortex. Nine animals were sacrificed 24 h, 3 days or 7 days after implantation of dialysis tubing. Although mild neuronal cell death and small petechial hemorrhages were seen in elose proximity to the implantation site, the striking finding was the presence of degenerating axons both adjacent to the implantation site and in remote sites such as the corpus callosum and contralateral hippocampus. The observed changes could alter brain function near or remote from the implantation site and should be considered in analysis of dialysis experiments.