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Molecular and Cellular Biology, June 2001, p. 3807-3819, Vol. 21, No. 11
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.11.3807-3819.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Loss of Hippocampal CA3 Pyramidal Neurons in Mice Lacking STAM1

Mitsuhiro Yamada,1,2 Toshikazu Takeshita,1 Shigeto Miura,1 Kazuko Murata,1,3 Yutaka Kimura,1 Naoto Ishii,1 Masato Nose,4 Hiroyuki Sakagami,5 Hisatake Kondo,5 Fumi Tashiro,6 Jun-Ichi Miyazaki,6 Hidetada Sasaki,2 and Kazuo Sugamura1,3,*

Department of Microbiology and Immunology,1 Department of Histology,5 and Department of Geriatric Medicine,2 Tohoku University School of Medicine, and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation,3 Sendai 980-8575, Second Department of Pathology, Ehime University School of Medicine, Ehime 791-0295,4 and Department of Nutrition and Physiological Chemistry, Osaka University Medical School, Suita 565-0871,6 Japan

Received 6 October 2000/Returned for modification 18 October 2000/Accepted 14 February 2001

STAM1, a member of the STAM (signal transducing adapter molecule) family, has a unique structure containing a Src homology 3 domain and ITAM (immunoreceptor tyrosine-based activation motif). STAM1 was previously shown to be associated with the Jak2 and Jak3 tyrosine kinases and to be involved in the regulation of intracellular signal transduction mediated by interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. Here we generated mice lacking STAM1 by using homologous recombination with embryonic stem cells. STAM1-/- mice were morphologically indistinguishable from their littermates at birth. However, growth retardation in the third week after birth was observed for the STAM1-/- mice. Unexpectedly, despite the absence of STAM1, hematopoietic cells, including T- and B-lymphocyte and other hematopoietic cell populations, developed normally and responded well to several cytokines, including IL-2 and GM-CSF. However, histological analyses revealed the disappearance of hippocampal CA3 pyramidal neurons in STAM1-/- mice. Furthermore, we observed that primary hippocampal neurons derived from STAM1-/- mice are vulnerable to cell death induced by excitotoxic amino acids or an NO donor. These data suggest that STAM1 is dispensable for cytokine-mediated signaling in lymphocytes but may be involved in the survival of hippocampal CA3 pyramidal neurons.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Phone: 81-22-717-8096. Fax: 81-22-717-8097. E-mail: sugamura{at}mail.cc.tohoku.ac.jp.

Molecular and Cellular Biology, June 2001, p. 3807-3819, Vol. 21, No. 11
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.11.3807-3819.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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