Abstract
The paternal or maternal mammalian X chromosome is inactivated (‘lyonization’) at random early in the development of the female embryo1,2. Once established, the inactivation of the chromosome is maintained in the cell and in all its descendants. However, spontaneous local reactivation of the inactive X chromosome is found at low frequency in human–mouse hybrid cells3,4. So far only the Xg locus5,6 and the locus for microsomal steroid sulphatase (sts)7 (both assigned to the short arm of the X chromosome), have been shown to escape inactivation. The locus for hypoxanthine phosphoribosyltransferase (hprt) is susceptible to inactivation8 and humans heterozygous for HPRT deficiency (the Lesch–Nyhan syndrome, L–N)9, show a mosaic pattern of HPRT activity in their cultured fibroblasts8. To investigate the molecular basis of X inactivation, we have used DNA isolated from each of the two subpopulations of a L–N heterozygote, to transform cultured HPRT-deficient mouse fibroblasts. Transformation of the mouse cells with the inactivated human hprt+ gene occurred with essentially the same efficiency as with the active human hprt+ gene. Thus, reactivation of the lyonized human hprt locus is possible after interspecific DNA-mediated gene transfer.
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de Jonge, A., Abrahams, P., Westerveld, A. et al. Expression of human hprt gene on the inactive X chromosome after DNA-mediated gene transfer. Nature 295, 624–626 (1982). https://doi.org/10.1038/295624a0
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DOI: https://doi.org/10.1038/295624a0
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