Age-dependent selection against hypoxanthine phosphoribosyl transferase-deficient cells in mouse haematopoiesis

The basis of a previously observed difference in the level of contribution of hypoxanthine phosphoribosyltransferase-deficient cells between the haematopoietic and non-haematopoietic tissues of chimaeric and heterozygous mice has been clarified by studying two populations of female mice that differ only in that one is heterozygous for a null allele at the hprt locus and the other is wild type at this locus. Both populations are heterozygous for an electrophoretic variant allele at the X-linked Pgk-1 locus, so that X-chromosome inactivation generates cells expressing different isozymes of phosphoglycerate kinase which can be assayed to monitor cell selection. The results show that hypoxanthine phosphoribosyltransferase deficiency itself, rather than an effect of another X-linked gene, causes a reduced level of contribution to haematopoietic tissues. Further, the extent of the depletion increases significantly with age, and this effect is due to a progressive reduction in the level of contribution to haematopoietic tissues rather than to an increase in the level of contribution to non-haematopoietic tissues.