Essential Roles of <i>Exocyst Complex Component 3-like 2</i> on Cardiovascular Development in Mice
Chisato Watanabe,
Hirotoshi Shibuya,
Yusuke Ichiyama,
Eiichi Okamura,
Setsuko Tsukiyama-Fujii,
Tomoyuki Tsukiyama,
Shoma Matsumoto,
Jun Matsushita,
Takuya Azami,
Yoshiaki Kubota,
Masahito Ohji,
Fumihiro Sugiyama,
Satoru Takahashi,
Seiya Mizuno,
Masaru Tamura,
Ken-ichi Mizutani,
Masatsugu Ema
Affiliations
Chisato Watanabe
Department of Stem Cells and Human Disease Models, Research Center for Animal Life Science, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan
Hirotoshi Shibuya
Technology and Development Team for Mouse Phenotype Analysis, RIKEN BioResource Research Center, Tsukuba 305-0074, Japan
Yusuke Ichiyama
Department of Ophthalmology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan
Eiichi Okamura
Department of Stem Cells and Human Disease Models, Research Center for Animal Life Science, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan
Setsuko Tsukiyama-Fujii
Department of Stem Cells and Human Disease Models, Research Center for Animal Life Science, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan
Tomoyuki Tsukiyama
Department of Stem Cells and Human Disease Models, Research Center for Animal Life Science, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan
Shoma Matsumoto
Department of Stem Cells and Human Disease Models, Research Center for Animal Life Science, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan
Jun Matsushita
Department of Stem Cells and Human Disease Models, Research Center for Animal Life Science, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan
Takuya Azami
Department of Stem Cells and Human Disease Models, Research Center for Animal Life Science, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan
Yoshiaki Kubota
Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan
Masahito Ohji
Department of Ophthalmology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan
Fumihiro Sugiyama
Laboratory Animal Resource Center in Transborder Medical Research Center, University of Tsukuba, Tsukuba 305-8575, Japan
Satoru Takahashi
Laboratory Animal Resource Center in Transborder Medical Research Center, University of Tsukuba, Tsukuba 305-8575, Japan
Seiya Mizuno
Laboratory Animal Resource Center in Transborder Medical Research Center, University of Tsukuba, Tsukuba 305-8575, Japan
Masaru Tamura
Technology and Development Team for Mouse Phenotype Analysis, RIKEN BioResource Research Center, Tsukuba 305-0074, Japan
Ken-ichi Mizutani
Laboratory of Stem Cell Biology, Graduate School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Japan
Masatsugu Ema
Department of Stem Cells and Human Disease Models, Research Center for Animal Life Science, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan
Angiogenesis is a process to generate new blood vessels from pre-existing vessels and to maintain vessels, and plays critical roles in normal development and disease. However, the molecular mechanisms underlying angiogenesis are not fully understood. This study examined the roles of exocyst complex component (Exoc) 3-like 2 (Exoc3l2) during development in mice. We found that Exoc3l1, Exoc3l2, Exoc3l3 and Exoc3l4 are expressed abundantly in endothelial cells at embryonic day 8.5. The generation of Exoc3l2 knock-out (KO) mice showed that disruption of Exoc3l2 resulted in lethal in utero. Substantial numbers of Exoc3l2 KO embryos exhibited hemorrhaging. Deletion of Exoc3l2 using Tie2-Cre transgenic mice demonstrated that Exoc3l2 in hematopoietic and endothelial lineages was responsible for the phenotype. Taken together, these findings reveal that Exoc3l2 is essential for cardiovascular and brain development in mice.
