Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor γ chain

Kazuyuki Ohbo, Toshio Suda, Motohiro Hashiyama, Akio Mantani, Mika Ikebe, Kazuhisa Miyakawa, Mako Moriyama, Masataka Nakamura, Motoya Katsuki, Kiyoshi Takahashi, Ken Ichi Yamamura, Kazuo Sugamura

Research output: Contribution to journalArticle

187 Citations (Scopus)

Abstract

The interleukin-2 (IL-2) receptor γ chain is indispensable for IL-2-, IL- 4-, IL-7-, IL-9-, and IL-15-mediated signaling. Mutations of the human γ chain cause the X-linked severe combined immunodeficiency (XSCID), showing that T and natural killer cells absolutely require the γ chain for their development in humans. To elucidate the roles of the y chain in hematopoiesis, we have generated mice, by gene targeting, that express a form of the γ chain lacking the cytoplasmic region. Male mice carrying the truncated γ-chain mutant, which mimics mutations in patients with XSCID, showed a decrease in the number of lymphocytes and an increase in monocytes; the number of T cells was profoundly reduced and no natural killer cells were detected, which is similar to the characteristic of human XSCID. Unlike human XSCID, the levels of B cells were also reduced. In spite of the severe decrease 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. Interestingly, the stem cell population with surface phenotypes of CD34, c-kit, and Sca-1 was significantly increased. Furthermore, the colony-forming 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 γ chain causes significant effects on the immunological system in mice.

Original languageEnglish
Pages (from-to)956-967
Number of pages12
JournalBlood
Volume87
Issue number3
Publication statusPublished - 1996 Feb 1

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X-Linked Combined Immunodeficiency Diseases
Interleukin-2 Receptors
Hematopoiesis
Cells
Modulation
Interleukin-9
Interleukin-15
Interleukin-7
T-cells
Lymphocytes
Stem cells
Interleukin-4
Interleukin-2
Immunoglobulin M
Assays
Genes
B-Lymphocytes
Mutation
Natural Killer T-Cells
Gene Targeting

ASJC Scopus subject areas

  • Hematology

Cite this

Ohbo, K., Suda, T., Hashiyama, M., Mantani, A., Ikebe, M., Miyakawa, K., ... Sugamura, K. (1996). Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor γ chain. Blood, 87(3), 956-967.

Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor γ chain. / Ohbo, Kazuyuki; Suda, Toshio; Hashiyama, Motohiro; Mantani, Akio; Ikebe, Mika; Miyakawa, Kazuhisa; Moriyama, Mako; Nakamura, Masataka; Katsuki, Motoya; Takahashi, Kiyoshi; Yamamura, Ken Ichi; Sugamura, Kazuo.

In: Blood, Vol. 87, No. 3, 01.02.1996, p. 956-967.

Research output: Contribution to journalArticle

Ohbo, K, Suda, T, Hashiyama, M, Mantani, A, Ikebe, M, Miyakawa, K, Moriyama, M, Nakamura, M, Katsuki, M, Takahashi, K, Yamamura, KI & Sugamura, K 1996, 'Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor γ chain', Blood, vol. 87, no. 3, pp. 956-967.
Ohbo K, Suda T, Hashiyama M, Mantani A, Ikebe M, Miyakawa K et al. Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor γ chain. Blood. 1996 Feb 1;87(3):956-967.
Ohbo, Kazuyuki ; Suda, Toshio ; Hashiyama, Motohiro ; Mantani, Akio ; Ikebe, Mika ; Miyakawa, Kazuhisa ; Moriyama, Mako ; Nakamura, Masataka ; Katsuki, Motoya ; Takahashi, Kiyoshi ; Yamamura, Ken Ichi ; Sugamura, Kazuo. / Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor γ chain. In: Blood. 1996 ; Vol. 87, No. 3. pp. 956-967.
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