title: Administration of factor XIII B subunit increased plasma factor XIII A subunit levels in factor XIII B subunit knock-out mice.
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.
authors.affiliation: Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Souri
authors.forename: Shiori
authors.initials: S
authors.lastname: Koseki-Kuno
authors.forename: Naoki
authors.initials: N
authors.lastname: Takeda
authors.forename: Jay L
authors.initials: JL
authors.lastname: Degen
authors.forename: Akitada
authors.initials: A
authors.lastname: Ichinose
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005176:Factor XIII / Q000235:genetics* / Q000502:physiology / Q000627:therapeutic use; D005177:Factor XIII Deficiency / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D005176:Factor XIII; C054380:factor XIIIb