MODULATION OF HEMATOPOIESIS IN MICE WITH A TRUNCATED MUTANT OF THE INTERLEUKIN-2 RECEPTOR-GAMMA CHAIN

The interleukin-2 (IL-2) receptor gamma chain is indispensable for IL- 2-, IL-4-, IL-7-, IL-9-, and IL-15-mediated signaling. Mutations of th e human gamma chain cause the X-linked severe combined immunodeficienc y (XSCID), showing that T and natural killer cells absolutely require the gamma chain for their development in humans, To elucidate the role s of the gamma chain in hematopoiesis, we have generated mice, by gene targeting, that express a form of the gamma chain lacking the cytopla smic region. Male mice carrying the truncated gamma-chain mutant, whic h mimics mutations in patients with XSCID, showed a decrease in the nu mber of lymphocytes and an increase in monocytes; the number of T cell s was profoundly reduced and no natural killer cells were detected, wh ich is similar to the characteristic of human XSCID. Unlike human XSCI D, the levels of B cells were also reduced. In spite of the severe dec rease in CD45R(+)/sIgM(+) B cells, the level of IgM in serum of the 8- week-old mutant mice was higher than that of control littermates. Inte restingly, the stem cell population with surface phenotypes of CD34, c -kit, and Sca-1 was significantly increased. Furthermore, the colony-f orming assay showed that the mutant mice had 15-fold higher numbers of hematopoietic progenitor cells in the spleen as compared with that of controls, These results indicate that functional loss of the gamma ch ain causes significant effects on the immunological system in mice. (C ) 1996 by The American Society of Hematology.