Novel genetic instability associated with a developmentally regulated glycosyltransferase locus in Chinese hamster...

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 less than or equal to 10(-7), while 5azaC treatment had no effect. Revertants were obtained at high frequency (approximately 10(-4)) and were found to belong to two classes. Three independent revertants gave rise to new LEC10 mutants at high frequency (approximately 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 revertant 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.