Loss of hippocampal CA3 pyramidal neurons in mice lacking STAM1

Mitsuhiro Yamada, Toshikazu Takeshita, Shigeto Miura, Kazuko Murata, Yutaka Kimura, Naoto Ishii, Masato Nose, Hiroyuki Sakagami, Hisatake Kondo, Fumi Tashiro, Jun Ichi Miyazaki, Hidetada Sasaki, Kazuo Sugamura

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3807-3819
Number of pages13
JournalMolecular and cellular biology
Volume21
Issue number11
DOIs
Publication statusPublished - 2001 Jun

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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