Novel genetic instability associated with a developmental regulated glycosyltransferase locus in Chinese hamster ovary cells

LEC10 is a dominant glycosylation mutant of Chinese hamster ovary (CHO) cells that expresses a developmentally regulated glycosyltransferase (GlcNAc-TIII) not detectable in parental CHO cells. Several mutagens were found to increase the frequency of LEC10 mutants up to 10-fold over the spontaneous frequency of ≤10^-7, while 5azaC treatment had no effect. Revenants were obtained at high frequency (∼10^-4) and were found to belong to two classes. Three independent revertants gave rise to new LEC10 mutants at high frequency (∼10^-4) while seven others gave new LEC10 mutants at the low frequency typical of unmutagenized parental CHO cells. No evidence of a general mutator phenotype was found in the revenant lines with a high rereversion frequency. The combined data suggest a novel form of genomic instability at the LEC10 locus in CHO cells. Genetic events that affect the expression of developmentally regulated glycosyltransferases may be identified by further studies of LEC10 and other dominant CHO glycosylation mutants.