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Thromb Haemost 2008; 99(02): 401-408
DOI: 10.1160/TH07-10-0599
Animal Models
Schattauer GmbH

Male-specific cardiac pathologies in mice lacking either the A or B subunit of factor XIII

Masayoshi Souri
1   Department of Molecular Patho-Biochemistry and Patho-Biology on Blood and Circulation, Yamagata University School of Medicine, Yamagata, Japan
,
Shiori Koseki-Kuno
1   Department of Molecular Patho-Biochemistry and Patho-Biology on Blood and Circulation, Yamagata University School of Medicine, Yamagata, Japan
,
Naoki Takeda
2   Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan
,
Mitsunori Yamakawa
3   Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan
,
Yasuchika Takeishi
4   Department of Internal Medicine I, Yamagata University School of Medicine, Yamagata, Japan
,
Jay L. Degen
5   Division of Developmental Biology, Children’s Hospital Research Foundation, Cincinnati, Ohio, USA
,
Akitada Ichinose
1   Department of Molecular Patho-Biochemistry and Patho-Biology on Blood and Circulation, Yamagata University School of Medicine, Yamagata, Japan
› Author Affiliations Financial support: 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 (USA, HL71555 and AR49822 to JLD).
Further Information

Publication History

Received: 08 October 2007

Accepted after major revision: 28 January 2007

Publication Date:
24 November 2017 (online)

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Summary

Factor XIII (FXIII) is a proenzyme of plasma transglutaminase consisting of enzymatic A subunits (FXIII-A) and non-catalytic B subunits (FXIII-B), and acts in haemostasis and wound healing. We generated mice lacking either FXIII-A or FXIII-B to investigate the physiological functions of FXIII in vivo. A longitudinal study was carried out using the gene-targeted mice to explore the possible effects of FXIII deficiency on aging. Survival rates of FXIII-A-/- males decreased to approximately 50% at 10 months after birth, although most FXIII-A-/- females and both genders of wild-type mice survived. Four FXIII-A-/- males died of severe intra-thoracic haemorrhage, and a large haematoma was found in their hearts. Haemorrhage, haemosiderin deposition and/or fibrosis were observed in the hearts of other dead FXIII-A-/- males. Fibrosis together with haemosiderin deposition was also found in the hearts of FXIII-A-/- males sacrificed. The in-vivo cardiac function was normal in FXIII-A-/- mice when compared with wild-type mice despite the presence of significant cardiac fibrosis. Although survival rates for both genders of the FXIII-B-/- and wild-type mice did not differ, mild fibrosis together with haemosiderin deposits were only found in the hearts of the sacrificed FXIII-B-/- males. Carditis and fibrosis in FXIII-deficient mice might be caused by a faulty or delayed reparative process that was initiated by abnormal haemorrhagic events within heart tissue. It is important therefore to examine possible cardiac involvement in human patients with congenital FXIII deficiency.

Keywords

Transglutaminase - haemostasis - wound healing - gene-targeting
 

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