Choice of the parent husbandry and sex of the offspring influence the extent of blood mosaicism [proportion of PIGA(−) cells] in lox-Piga-lacZ x EIIa-cre offspring: Thelox-Piga-lacZ gene follows an X-linked inheritance pattern. Male offspring of the EL breeding therefore do not inherit alox-Piga-lacZ gene and therefore do not undergo Pigagene recombination. The expression of Cre determines the time span during which Piga gene recombination may occur. If maternally derived, EIIa promoter activity starts already in the oocyte and ceases around day E4.5. In contrast, if paternally derived, Cre expression starts at the time when male gene expression is initiated which is around E2.5. The contribution of PIGA(−) cells to hematopoiesis depends on the contribution of PIGA(−) cells to the stem cell pool. Male PIGA(−) cells are subject to early negative selection.43 In female cells however, the PIGA(−) phenotype is only expressed after the wild-type Piga gene has been inactivated by X chromosome inactivation. Selection against PIGA(−) cells starts therefore later in ontogenesis. This explains the higher contribution of PIGA(−) hematopoietic cells found in female mice compared to male mice from the same breeding and compared to the PIGA(−) cell contribution previously reported in chimeric mice obtained after injection of PIGA(−) XY ES cells.13,14 For the LE breeding only the offspring carrying a lox-Piga-lacZgene are illustrated. The genotype is shown in italics, pindicates paternally derived, m maternally derived genes.