SOMATIC CELL GENETIC ANALYSIS OF INTERFERON PRODUCTION AND RESPONSE *

Somatic cell genetic techniques have permitted the analysis of gene arrangement in cultured mammalian cells. Hybrid cells produced by the fusion of cells from two different species generally lose chromosomes from one parental input preferentially. This segregation provides the basis for mapping genes to specific chromosomes for the species whose chromosomes are lost.' Synteny assignments can be made by correlating the presence of marker isozymes and the gene to be mapped. Identification of specific chromosomes retained in a hybrid through the use of differential staining and banding techniques is then used for the assignment of the gene to a particular chromosome. The interferon system is amenable to somatic cell genetic analysis since species-specificity of interferon action allows the study of interferon production and response in interspecific heterokaryons and hybrids.' Both interferon synthesis and the attainment of the antiviral state after interferon treatment are inducible functions, requiring de novo RNA and protein systhesis. The genes governing these two functions are located on different chromosomes in the species that have been ~ t u d i e d . ~ Human/mouse and human/Chinese hamster hybrid cells, which usually segregate human chromosomes, have been used to map genes involved in the human interferon system. Sensitivity to human interferon is governed by human chromosome 21.4.5 The exact nature of the chromosome 21-coded gene product responsible for conferring interferon sensitivity is unknown, but current models postulate that a cell surface receptor is involved in the species-specific interferon response.' Trisomy 21 cells are markedly more sensitive to human interferon than normal diploid fibroblasts, while monosomy 21 cells are less ~ens i t i ve .~ Genes that govern the synthesis of human fibroblast interferon have been assigned to three human chromosomes (2 ,s and 9)?-" The roles played by each of these chromosomes are as yet unclear, but it is possible that multiple interferon structural loci exist. In this report, we will discuss our recent work with somatic cell hybrids to further elucidate the genetic control behind interferon systhesis and response.