Molecular mechanisms of extinction of liver-specific functions in mouse hepatoma rat fibroblast hybrids: extinction of alpha-fetoprotein gene.

Somatic cell hybrids formed by the fusion of mouse hepatoma (BWTG3) and rat fibroblast (JF1) cells exhibit the extinction of mouse AFP gene expression. Analysis of HindIII digests clearly shows that both mouse and rat AFP genes are present in the hybrids. DNA-RNA hybridization data show that AFP mRNA is virtually absent in the somatic cell hybrids. Our studies indicate, therefore, that extinction of mouse AFP gene expression in somatic cell hybrids (BJ01, BJ50, and BJ140) occurs in the presence of the rat genes and that the mechanism of extinction involves processes that result in the loss of AFP mRNA. We propose that the mechanism may involve either the inhibition of transcription or an inhibition of the processing of the mRNA transcript.