Murine haematopoiesis: studies using X chromosome-inactivation mosaics

Abstract

Blood erythrocytes and leukocytes were serially sampled over many months from female mice that were heterozygous at the X-chromosomal locusencoding the glycolytic enzyme phosphoglycerate kinase (PGK-1). PGK-1A andPGK-1B alloenzymes were identified and quantified electrophoretically. There was little variation in PGK-1 phenotype between serial samples from individual mice. This small amount of variation was discussed in terms of the number of clones participating in haematopoiesis and the contribution of technical factors.

Similar studies were performed using radiation chimaeras, repopulated with either a high dose (107 cells) or a low dose (105 cells) of PGK-1AB bonemarrow. The variation in PGK-1 phenotype between serial samples taken fromthe animals repopulated with a high dose of bone marrow was comparable to that seen in normal animals. In contrast, the variation observed in the low- dose chimaeras was. relatively large. These animals were used to study the clonal organisation of the haematopoietic system.

The development of B lymphocytes carrying the X-linked immunodeficiency mutation (xid) was studied in mice that were heterozygous at both the x[d and the Pgk-1 loci.

An abnormallly large population of B lymphocytes, possessing an characteristic membrane phenotype, was observed in the peripheral blood of a group of experimental mice. This behaved as a transplantable neoplasia. Subsequently, similar populations were found in several aged (>2 years) CBA/Ca mice. A preliminary characterisation of these cells was carried out and their possible relevance to human chronic lymphocytic leukaemia (CLL) was discussed.