title: The clock gene Per2 is required for normal platelet formation and function.
abstract: BACKGROUND
  Apoptotic cell death is a highly regulated genetic program, which has been observed in mature megakaryocytes fragmenting into platelets. The clock gene Per2, a key component of core clock oscillator, was involved in affecting both cell cycle control and apoptosis. Thus, loss of Per2 function may be considered potential influence of platelet formation and function.
  
  
  METHODS
  Per2-null mice and C57BL/6 mice were used in the study. Bleeding time, platelet count, megakaryocyte count, megakaryocyte ploidy, megakaryocyte apoptosis, rate of proplatelet formation, clot retraction, platelet aggregation and secretion were performed to evaluate thrombopoiesis and hemostasis. Quantitative RT-PCR was employed to analyze genes expression in liver, bone marrow and enriched megakaryocytes.
  
  
  RESULTS
  The Per2-null mice had nearly 50% platelet counts in peripheral blood. Per2-null platelets were compromised in their ability to aggregate and secretion, consistent with a marked reduction in the number of dense and a-granules. Megakaryocytes from Per2-null mice showed no significant variation in number but increased in ploidy. Ultrastructural examination of Per2-null megakaryocytes revealed many vacuoles in demarcation membranes and reduction in platelet granules. Megakaryocytes from Per2-null bone marrow decreased the rate of proplatelet formation and impaired apoptosis. Per2-null mice showed increased both in Tpo in livers and its receptors C-mpl in bone marrow, and the megakaryocytes from these mice decreased P53 expression, consequently increased Bcl-xl and Bcl-2 level.
  
  
  CONCLUSIONS
  The clock gene Per2 modulating the apoptosis of megakaryocytes was required for platelet formation and function.
authors.affiliation: Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shiming
authors.initials: S
authors.lastname: Wang
authors.forename: Zichun
authors.initials: Z
authors.lastname: Hua
authors.forename: Jianfa
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology*; D002940:Circadian Rhythm / Q000235:genetics; D008533:Megakaryocytes / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D056950:Period Circadian Proteins / Q000097:blood* / Q000172:deficiency / Q000235:genetics
chemical_list: C513312:Per2 protein, mouse; D056950:Period Circadian Proteins