title: C1galt1-deficient mice exhibit thrombocytopenia due to abnormal terminal differentiation of megakaryocytes.
abstract: C1galt1 is essential for synthesis of the core 1 structure of mucin-type O-glycans. To clarify the physiological role of O-glycans in adult hematopoiesis, we exploited the interferon-inducible Mx1-Cre transgene to conditionally ablate the C1galt(flox) allele (Mx1-C1). Mx1-C1 mice exhibit severe thrombocytopenia, giant platelets, and prolonged bleeding times. Both the number and DNA ploidy of megakaryocytes in Mx1-C1 bone marrow were similar to those in wild-type (WT) mice. However, there were few proplatelets in Mx1-C1 primary megakaryocytes. Conversely, bone marrow transplanted from Mx1-C1 to WT and splenectomized Mx1-C1 mice gave rise to observations similar to those described above. The expression of GPIbα messenger RNA was unchanged in Mx1-C1 bone marrow, whereas flow cytometric and western blot analyses using megakaryocytes and platelets revealed that the expression of GPIbα protein was significantly reduced in Mx1-C1 mice. Moreover, circulating Mx1-C1 platelets exhibited an increase in the number of microtubule coils, despite normal levels of α- and β-tubulin. Our observations suggest that O-glycan is required for terminal megakaryocyte differentiation and platelet production and that the decrease in GPIbα in cells lacking O-glycan might be caused by increased proteolysis.
authors.affiliation: Department of Anatomy and Embryology, University of Tsukuba, Tennodai, Tsukuba, Ibaraki, Japan. t-kudo@md.tsukuba.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Kozue
authors.initials: K
authors.lastname: Hagiwara
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Kozuma
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Ikehara
authors.forename: Michito
authors.initials: M
authors.lastname: Hamada
authors.forename: Ken
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Ema
authors.forename: Soichiro
authors.initials: S
authors.lastname: Murata
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ohkohchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D005700:Galactosyltransferases / Q000235:genetics* / Q000502:physiology; D018014:Gene Transfer Techniques; D008297:Male; D055016:Megakaryocyte Progenitor Cells / Q000378:metabolism / Q000502:physiology; D008533:Megakaryocytes / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013921:Thrombocytopenia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D034061:Thrombopoiesis / Q000235:genetics
chemical_list: C515597:C1galt1 protein, mouse; D005700:Galactosyltransferases