Preferential loss or inactivation of chromosome Z4 APRT allele in CHO cells

In CHO cells, heterozygotes for the adenine phosphoribosyltransferase (APRT) locus arise spontaneously at high frequencies. However, such heterozygotes always yield APRT- mutants at low spontaneous rates. In an attempt to determine whether differences in the genomic environments of the two CHO APRT alleles might render one gene more susceptible to high-frequency spontaneous inactivation or deletion, we have mapped the functional APRT allele in four different spontaneous APRT heterozygotes. In each case, the functional APRT gene was found to reside on the Z7 chromosome; it was always the Z4 APRT allele that had been lost or inactivated. Two of these heterozygotes were shown to be physically hemizygous while the other two retained two copies of the APRT gene, indicating that the high-frequency event can involve either spontaneous deletion or inactivation.