Localized Derepression on the Human Inactive X Chromosone in Mouse-Human Cell Hybrids.
Evidence for derepression of the gene for hypoxanthine phosphoribosyltransferase (HPRT; IMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) on the human inactive X chromosome was obtained in hybrids of mouse and human cells. The mouse cells lacked HPRT and were also deficient in adenine phosphoribosyltransferase (APRT; AMP: pyrophosphate phosphoribosyltransferase; EC2.4.2.7). The human female fibroblasts were HPRT-deficient as a consequence of a mutation on the active X but contained a normal HPRT gene on the inactive X. The two human X chromosomes were further distinguished by differences in morphology: the inactive X was morphologically normal while the active X included most of the long arm of autosome no. 1 translocated to the distal end of the X long arm. Forty-one hybrid clones were first isolated by selection for the presence of APRT; when these clones were selected for HPRT, six of them yielded derivatives having human HPRT with incidences of about 1 in 10-6 APRT-selected hybrid cells. The HPRT-positive derivatives contained a normal-appearing X chromosome indistinguishable from the inactive X of the parental human fibroblasts. The active X with the translocation was not found in any of the HPRT-positive hybrid cells. Human phosphoglycerokinase (ATP:3-phospho-D-glycerate 1-phosphotransferase. EC 2.7.2.3) and glucose-6-phosphate dehydrogenase (D-glucose 6-phosphate: NADP 1-oxidoreductase, EC 1.1.1.49), which are specified by X-chromosomal loci, were not detected in the hybrids expressing HPRT even though they contained an apparently intact X chromosome. The observations are most simply explained by the infrequent, stable derepression of inactive X chromosome segments  that include the HPRT locus but not the phosphoglycerokinase and glucose-6-phosphate dehydrogenase loci.
D000228:Adenine Phosphoribosyltransferase / Q000378:metabolism; D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D002999:Clone Cells; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D007621:Karyotyping; D051379:Mice; D008856:Microscopy, Fluorescence; D011233:Precipitin Tests; D011796:Quinacrine; D011817:Rabbits / Q000276:immunology; D012730:Sex Chromosomes / Q000378:metabolism* / Q000648:ultrastructure; D013489:Suppression, Genetic
D000228:Adenine Phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase; D011796:Quinacrine