Human-mouse hybrid cell lines containing partial complements of human chromosomes and functioning human genes.

This paper will describe the isolation and properties of a group of new somatic hybrid cell lines obtained by crossing human diploid fibroblasts with an established mouse fibroblast line. These hybrids represent a combination between species more remote than those previously described (see, however, discussion of virusinduced heterokaryons). They are also the first reported hybrid cell lines containing human components and possess properties which may be useful for certain types of genetic investigations. Interspecific hybridizations involving rat-mouse,' hamster-mouse,2' and Armenian hamster-Syrian hamster4 combinations have been shown to yield populations of hybrid cells capable of indefinite serial propagation. Investigations of the karyotype and phenotype of such hybrids have shown that both parental genomes are present2' 5 and functional.6 In every case, some loss of chromosomes has been observed; this occurred primarily during the first few months of propagation, usually amounted to approximately 10-20 per cent of the complement present in newly formed hybrid cells, and involved chromosomes of both parents. Recent studies have provided evidence of preferential loss of chromosomes of one parental species in interspecific hybrids.2' A more extreme example of this preferential loss has been encountered in the human-mouse hybrid lines to be described, in which at least 75 per cent, and in some cases more than 95 per cent, of the human complement has been lost. It has been possible to relate the human characteristics of the hybrid phenotype to the number of human chromosomes retained. This has been shown for the colonial morphology of the hybrid and for the human antigens in the hybrid cell membrane, which were detected by mixed cell agglutination. Furthermore, information has been obtained with respect to the chromosomal localization of the thymidine kinase gene.