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Originally published online as doi:10.1189/jlb.1006638 on April 24, 2007

Published online before print April 24, 2007
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(Journal of Leukocyte Biology. 2007;82:429-435.)
© 2007 by Society for Leukocyte Biology

Large defects of type I allergic response in telomerase reverse transcriptase knockout mice

Azusa Ujike-Asai*, Aki Okada*, Yuchen Du*, Mitsuo Maruyama*, Xunmei Yuan{dagger}, Fuyuki Ishikawa{dagger}, Yoshiharu Motoo{ddagger}, Kenichi Isobe*,§ and Hideo Nakajima*,{ddagger},1

* Department of Basic Gerontology, National Institute for Longevity Sciences, Obu, Japan;
{dagger} Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kyoto, Japan;
{ddagger} Department of Medical Oncology, Kanazawa Medical University, Uchinada, Japan; and
§ Department of Immunology, Graduate School of Medicine, Nagoya University, Nagoya, Japan

1 Correspondence: Department of Medical Oncology, Kanazawa Medical University, Daigaku 1-1, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293, Japan. E-mail: hideonak{at}kanazawa-med.ac.jp

Telomerase is critically important for the maintenance of a constant telomere length, which in turn, is related to the concepts of longevity and oncogenesis. In addition, it has been well documented that telomerase activity is expressed in immune cells in a highly regulated manner. We have studied systemic anaphylaxis in mouse telomerase reverse transcriptase knockout (mTERT–/–) mice to understand the significance of telomerase activity and telomere stability in mast cells, which induce a type I allergic response. Compared with wild-type mice, mTERT–/– mice displayed largely attenuated, IgE-mediated, passive anaphylactic responses, which were observed even in the early generations of mTERT–/– mice, and had decreased numbers of mast cells in vivo and impaired development of bone marrow-derived mast cells (BMMCs) induced by IL-3 or stem cell factor in vitro. Moreover, in mTERT–/– mice, BMMCs exhibited a large morphology and low proliferation rate, while they possessed a comparable degranulation capacity and cell surface expression level of c-kit and Fc{epsilon}RI. These findings imply that telomerase activity has a definitive impact on the type I allergic response by altering the character of effecter mast cells.

Key Words: anaphylaxis • mast cell • TERT