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Development of peripheral lymphoid organs and natural killer cells depends on the helix–loop–helix inhibitor Id2

Nature volume 397, pages 702–706 (1999)Cite this article

Abstract

Transcription factors with a basic helix–loop–helix (HLH) motif have been shown to be crucial for various cell differentiation processes during development of multicellular organisms1. Id proteins inhibit the functions of these transcription factors in a dominant-negative manner by suppressing their heterodimerization partners through the HLH domains2,3,4. Members of the Id family also promote cell proliferation4,5, implying a role in the control of cell differentiation. Here we show that Id2 is indispensable for normal development of mice. Id2−/− mice lack lymph nodes and Peyer's patches. However, their splenic architecture is normal, exhibiting T-cell and B-cell compartments and distinct germinal centres. The cell population that produces lymphotoxins, essential factors for the development of secondary lymphoid organs6,7,8,9,10,11, is barely detectable in the Id2−/− intestine. Furthermore, the null mutants show a greatly reduced population of natural killer (NK) cells, which is due to an intrinsic defect in NK-cell precursors. Our results indicate that Id2 has an essential role in the generation of peripheral lymphoid organs and NK cells.

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Figure 1: Generation of Id2-null-mutant mice by targeted inactivation.
Figure 2: Retarded growth of Id2−/− mice.
Figure 3: Lymph nodes and Peyer's patches are absent in Id2−/− mice.
Figure 4: Normal splenic architecture of the Id2−/− mice.
Figure 5: Impaired NK-cell production in the Id2−/− mice.
Figure 6: RT-PCR analysis on Id2 expression in CD4+CD3−IL-7Rα+ and NK cells.

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Acknowledgements

We thank H. Yoshida, N. Mitato, M. Matsumoto, T. Yamada, S. Takeda, K.Ogasawara and R. Benezra for valuable discussions and suggestions; T. Yagi, T. Neuman, S. Itohara, H. Yoshida, T. Takemori, M. Miyasaka, T. Nishimura, E. Nakamura, N. Minato, H. Kawamoto and Y.Katsura for providing materials; R. Liebal for supporting the mouse work; J. Krull, Y. Tsuji, S.-H. Park, M. Tanji, T. Kikuchi and M. Hirashima for assistance; and R. Altschäffel for photographic work. This work was supported by the Max-Planck Soceity, the Ministry of Education, Science and Culture of Japan, and the Yamanouchi Foundation. Y.Y. was supported by the Alexander von Humboldt Foundation, the Jeantet-Foundation and the Human Frontier Science Program.

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Authors and Affiliations

  1. Department of Molecular Cell Biology, Max-Planck Institute of Biophysical Chemistry, Am Fassberg, 37077, Göttingen, Germany

    Yoshifumi Yokota, Ahmed Mansouri & Peter Gruss

  2. Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Shogoin Kawahara-cho 53, Sakyo-ku, 606-8507, Kyoto, Japan

    Yoshifumi Yokota, Seiichi Mori, Seiichi Sugawara, Satoko Adachi & Shin-Ichi Nishikawa

  3. Department of Neurology and Psychiatry, School of Medicine, Gifu University, Tsukasa-machi 40, Gifu, Japan

    Seiichi Sugawara & Satoko Adachi

  4. Integrative Projects, Mitsuibishi Kasei Institute of Life Sciences Minami-Ooya 11, Machida-shi, 194-8511, Tokyo, Japan

    Seiichi Sugawara & Satoko Adachi

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Correspondence to Yoshifumi Yokota.

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Yokota, Y., Mansouri, A., Mori, S. et al. Development of peripheral lymphoid organs and natural killer cells depends on the helix–loop–helix inhibitor Id2. Nature 397, 702–706 (1999). https://doi.org/10.1038/17812

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