1. ¹Laboratory of Molecular and Cellular Pathology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
2. ²Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka, Japan
3. ³Department of Laboratory Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
4. ⁴Department of Molecular Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
5. ⁵Department of Developmental Biology, Center for Translational and Advanced Animal Research on Human Disease, Graduate School of Medicine, Tohoku University, Aobaku, Sendai, Japan
6. ⁶Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Correspondence: Professor S Tanaka, MD, PhD, Laboratory of Molecular and Cellular Pathology, Hokkaido University School of Medicine, N 15, W 7, Kita-ku, Sapporo 060-8638, Japan. E-mail: tanaka@med.hokudai.ac.jp

^*Current address: Hirofumi Sawa, Department of Pathobiology, Hokkaido University Zoonosis Research Center, and 21st Century COE Program for Zoonosis Control, N12, W9, Sapporo, Japan

^†Current address: Kazuo Nagashima, Sapporo Higashi Tokushukai Hospital, N33, E13, Sapporo, Japan

Received 25 January 2009; Revised 22 February 2009; Accepted 27 February 2009; Published online 30 March 2009.

Abstract

SYT–SSX protein, resulted from chromosomal translocation, causes synovial sarcoma, which is a malignant tumor accounting for 10% of soft tissue sarcoma. However, biological functions of SYT (synovial sarcoma translocation), also known as SS18, are largely unclear, whereas it has been proven that Syt-null mice die at early stages of embryonic development. Here, we generated Syt-deficient mice and confirmed the reported phenotypes, including growth retardation, open neural tube and haplo-insufficient lethality, and therefore, there is no doubt that Syt is essential for embryonic development. However, placental defects, described in the earlier report, were rarely seen in our mice and we frequently observed cardiac defect in Syt-deficient mice. As the mechanisms responsible for embryonic lethality seem to be complicate, we performed additional experiments. By using primary cultured embryonic fibroblasts, we showed that Syt^-/- MEFs deregulate actin organization and suppressed cell migration. These observations suggest that Syt may contribute to the signaling pathway important for various cellular functions in vivo and in vitro, and we propose that Syt-deficient MEFs would be a powerful means to understand the biological roles of SYT in vitro.