The ability of mammalian cells to take up exogenously added DNA and to express genes included on that DNA has been well documented. DNA-mediated gene transfer (DMGT) potentially is a useful technique for the elucidation of many of the factors that control gene expression, and for the purification and isolation of mammalian genes. Before many of the benefits can be realized, however, a more detailed understanding of the organization, intracellular location, and expression of transferred genes will be needed. Recent studies have begun to characterize the DMGT process. Selected genes become linked to other exogenously added DNA during or subsequent to transfer and persist in the nuclei of recipient cells as part of large molecules called transgenomes. Transgenomes initially are maintained unstably and are lost from the population with first order kinetics. After a variable number of generations in culture, subpopulations arise that maintain the transferred genes stably. In these "stable" cells the transgenome is associated with a recipient cell chromosome, although the particular chromosome differs in independent "stable" lines. Mixture of an excess of specific nonselectable genes with the selected gene prior to transfer results in the inclusion of the nonselected genes in the transgenomes present in most cells that survive selection. This finding demonstrates the feasibility of introducing virtually any purified gene into mammalian cells. Recently microinjection of DNA directly into the nuclei of cells has been demonstrated. This technique greatly increases the frequency of gene transfer and significantly expands the number of cell types that can be genetically transformed.

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Two homoeo box loci mapped in evolutionarily related mouse and human chromosomes.

The homoeo box is a 180-base pair (bp) DNA sequence conserved in Drosophila homoeotic genes, which regulate early development. These DNA sequences are present in open reading frames and have been identified in specific gene transcripts in Drosophila and Xenopus embryos; they possess structural features in common with genes encoding some DNA-binding proteins. Homologous homoeo box sequences have been detected in species ranging from insects and annelids to vertebrates. The high degree of sequence conservation (70-90%) among different species suggests a strong evolutionary relationship and implies a common role in embryonic development. To test this hypothesis, one approach we have used is to examine the patterns of genetic organization of homoeo box sequences in mouse and human for any similarities; the second approach is to localize the chromosomal map positions of homoeo box sequences in the two species. A similar genomic organization and chromosomal distribution of homoeo box sequences would argue for a conserved function and might shed light on their mechanism of action. Here, we describe experiments which show that two homoeo box loci map, respectively, to evolutionarily related regions on mouse chromosome 11 and human chromosome 17.

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Spatial restriction in expression of a mouse homoeo box locus within the central nervous system.

A common feature of Drosophila homoeo box genes appears to be their spatially restricted expression patterns during morphogenesis. Using Northern blot analysis and in situ hybridization to mouse tissue sections, the spatially restricted expression of a newly identified mouse homoeo box locus, Hox-3, within the central nervous system of newborn and adult mice has been demonstrated.

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