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Administration of factor XIII B subunit increased plasma factor XIII A subunit levels in factor XIII B subunit knock-out mice

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Abstract

Factor XIII (FXIII) is a proenzyme of plasma transglutaminase consisting of enzymatic A (FXIII-A) and noncatalytic B subunits (FXIII-B), and acts in hemostasis and wound healing. We freshly generated mice lacking either FXIII-A or FXIII-B to investigate the physiological functions of FXIII in vivo. Mice carrying the disrupted allele were born at the expected Mendelian ratios, and the homozygous mice were viable and fertile under specific pathogen-free conditions. Although all homozygous and heterozygous mice showed no marked difference from the wild-type animals in general appearance, homozygous mice of either FXIII-A- or FXIII-B-deficiency did have prolonged bleeding times. It was confirmed that thrombin-dependent amine incorporation and fibrin-crosslinking in plasma were undetectable in the FXIII-A-deficient mice and markedly reduced in the FXIII-B-deficient mice; however, the gene expression of each subunit was regulated independently. Recombinant human FXIII-B (rFXIII-B) was expressed in a baculovirus expression system. When rFXIII-B was injected into FXIII-B-deficient mice, FXIII-A levels, fibrin crosslinking, and amine-incorporation activities increased in their plasma, indicating that FXIII-B assisted the maintenance of FXIII-A levels in the circulation. These mouse strains will be useful in exploring the possible pathophysiological roles of each subunit in vivo.

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Acknowledgments

This study was presented in part at the 9th Blood Agora Conference, Tokyo, Japan, August 2001, at the 1st Japan-Hungary Joint Conference on Transglutaminases, Yamagata, Japan, October 2001, at the 2nd Asian-Pacific Congress on Thrombosis and Hemostasis, Seoul, Korea, April 2002, at the 76th annual meeting of the Japanese Biological Society, Yokohama, Japan, October 2003, at the 26th annual meeting of the Japanese Society of Thrombosis and Hemostasis, Tokyo, Japan, November 2003, and at the 20th International Society on Thrombosis and Hemostasis, Sydney, Australia, August 2005. We are greatly indebted to Ms. Sandy Falcon from the Transgenic Mouse Laboratory at The Children’s Hospital Research Foundation for the injection of ES cells into blastcysts to generate FXIII-A KO mice, and Profs. K. Yamanishi of Hyogo Medical School and J. Takeda of Osaka Univ. for providing invaluable information and materials. We also thank Drs. Hiroki Iwata and Hirofumi Sugawara for invaluable discussion, Ms. Kathryn Talmage at The Children’s Hospital Research Foundation, and Mr. Tunekata Ito at Yamagata University for the animal care. This study was supported in part by research grants from The Ministry of Education, Science and Culture, Japan (10470205), The Uehara Memorial Foundation (Japan), The NOVARTIS Foundation for the Promotion of Science (Japan), The Daiwa Health Foundation (Japan), The Yamanouchi Foundation for Research on Metabolic Disorders (Japan), and The National Institutes of Health. M.S. performed research, analyzed data, and wrote the paper. S.K-.K., and N.T. performed research and analyzed data. J.L.D. analyzed data, and wrote the paper. A.I. designed the research, analyzed data, and wrote the paper.

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Authors and Affiliations

  1. Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Iida-Nishi 2-2-2, Yamagata, 990-9585, Japan

    Masayoshi Souri, Shiori Koseki-Kuno & Akitada Ichinose

  2. Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan

    Naoki Takeda

  3. Division of Developmental Biology, Children’s Hospital Research Foundation, Cincinnati, OH, USA

    Jay L. Degen

Authors
  1. Masayoshi Souri
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  2. Shiori Koseki-Kuno
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  3. Naoki Takeda
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  4. Jay L. Degen
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  5. Akitada Ichinose
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Correspondence to Akitada Ichinose.

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Souri, M., Koseki-Kuno, S., Takeda, N. et al. Administration of factor XIII B subunit increased plasma factor XIII A subunit levels in factor XIII B subunit knock-out mice. Int J Hematol 87, 60–68 (2008). https://doi.org/10.1007/s12185-007-0005-z

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  • DOI: https://doi.org/10.1007/s12185-007-0005-z

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