International Journal of Hematology

DOI: 10.1007/s12185-017-2394-y Pages: 428-435

Vwf K1362A resulted in failure of protein synthesis in mice

1. Nagoya University Hospital, Department of Medical Technique

2. Nagoya University Graduate School of Medicine, Department of Pathology and Clinical Laboratories

3. Nagoya University Hospital, Department of Transfusion Medicine

4. Nagoya University Hospital, Department of Clinical Laboratory

5. Research Institute for Microbial Diseases, Department of Experimental Genome Research

6. Keio University School of Medicine, Department of Molecular Biology

7. Nagoya University Graduate School of Medicine, Department of Pathophysiological Laboratory Sciences

Correspondence to:
Nobuaki Suzuki
Tel: +81-52-744-2652



Von Willebrand factor (VWF) is synthesized in megakaryocytes and endothelial cells (ECs) and has two main roles: to carry and protect coagulation factor VIII (FVIII) from degradation by forming VWF–FVIII complex; and to mediate platelet adhesion and aggregation at sites of vascular injury. Previous research using the HEK293 cell line revealed that the VWF K1362 mutation interacted directly with platelet glycoprotein Ib (GPIb). Vwf K1362A knock-in (KI) mice were therefore generated to verify the in vivo function of residue 1362 in binding to platelet GPIb. The Cre-loxP system was employed to introduce the Vwf K1362A mutation systemically in mice. In blood coagulation analysis, the VWF antigen (VWF:Ag) of Lys1362Ala KI homozygous (homo) mice was below the sensitivity of detection by enzyme-linked immunosorbent assay. FVIII activities (FVIII:C) were 47.9 ± 0.3 and 3.3 ± 0.3% (K1362A heterozygous (hetero) and K1362A KI homo mice, respectively) compared to wild-type mice. Immunohistochemical staining analysis revealed that VWF protein did not exist in ECs of K1362A KI homo mice. These results indicated that VWF protein synthesis of K1362A was impaired after transcription in mice. K1362 seems to represent a very important position not only for VWF function, but also for VWF synthesis in mice.

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