Growth Competition between W Mutant and Wild-type Cells in Mouse Aggregation Chimeras: (aggregation chimera/W mutation/c-kit oncogene/celluler competition/mouse).

The dominant spotting (W) locus of the mouse has been demonstrated to be identical with the c-kit proto-oncogene. The c-kit is strongly expressed in hematopoietic organs and the brain of mice. In homozygotes and double heterozygotes of the W mutant alleles (hereafter W mutant), development of erythrocytes, mast cells, melanocytes and germ cells is deficient. The deficiency of erythrocytes, mast cells and melanocytes is attributed to a defect of precursor cells, but the cause of the germ cell deficiency is not clear. We investigated the effect of the W mutation on proliferative potential of cells composing various organs by examining aggregation chimeras between W mutant and wild-type (+/+) embryos. Proportions of +/+ components were significantly greater in the male germ cells and hematopoietic cells. In contrast, the average proportions of +/+ components were comparable to those of W mutant components in other organs including the brain. The present result suggests that the W (c-kit) gene plays an important role in development of the male germ cells and hematopoietic cells and that it does not promote the proliferation of major cell population in the brain, in spite of the strong expression of the W (c-kit) gene in the brain.

Kidney Proximal Tubule Cells Originate from Approximately Four Progenitor Cells and Make Distinct Patches in Mouse Aggregation Chimeras: (aggregation chimera/kidney proximal tubule/beige mouse/pool size/patch size).

Giant lysosomal granules of bgJ /bgJ mutant mice were used as a marker to investigate the histological composition of kidney proximal tubule cells. Embryos of the bgJ /bgJ genotype and those of the +/+ genotype were aggregated, and lysosomes of their proximal tubule cells were histochemically stained with the ß-glucuronidase activity. Tubules composed of bgJ /bgJ -type epithelial cells alone, tubules composed of +/+-type epithelial cells alone and tubules containing both types of epithelial cells were observed in cross sections. When the long straight portion of proximal tubules was reconstructed from serial sections, most of the tubules were of the mixed type, and distinct patches of bgJ /bgJ -type or +/+-type epithelial cells were detectable. These patches appeared to extend to the longitudinal rather than the circumferential direction. This suggests the clonal proliferation followed the mixing of embryonic progenitor cells for proximal tubule cells. Estimation from proportions of bgJ /bgJ -type proximal tubules in total examined proximal tubules gave a pool size of approximately four primordial precursor cells for proximal tubules in both right and left kindeys. The fact that the proportion of bgJ /bgJ -type components was comparable between the right and left kidneys of each chimera suggests that all proximal tubule cells in both right and left kidneys may originate from common primordial precursor cells.