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Lancet. 2015 Feb 26;385 Suppl 1:S39. doi: 10.1016/S0140-6736(15)60354-3.

Use of a novel floxed mouse to characterise the cellular source of plasma coagulation FXIII-A.

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Leeds Institute of Cardiovascular & Metabolic Medicine, University of Leeds, Leeds, UK. Electronic address:
Leeds Institute of Cardiovascular & Metabolic Medicine, University of Leeds, Leeds, UK.
Division of Experimental Medicine, University of Montreal, Montreal, QC, Canada.
Department of Haematology, University of Cambridge, Cambridge, UK.
Division of Cancer and Haematology, Walter and Eliza Hall Institute, Melbourne, VIC, Australia.



Coagulation factor XIII-A has a crucial role in thrombus stabilisation and tissue repair. Factor XIII-A deficiency causes a severe bleeding phenotype and impaired wound healing, but the cellular origin of Factor XIII-A is unknown. To identify the cells that maintain the plasma pool, we generated a mouse floxed in coding exon7 of the factor XIII-A gene (F13A1). These mice were crossed with mice transgenic for Pf4-Cre-recombinase (thrombopoietic deletion) or Cd11b-Cre-recombinase (myeloid deletion). The resultant mice were compared with a Mpl-/- (thrombopoietin receptor knockout) thrombocytopenic murine model.


Factor XIII-A recombination was evaluated by quantitative PCR assay of genomic DNA from liver and spleen. Factor XIII-A enzyme activity was measured in plasma and platelets with a biotin incorporation assay. quantitative PCR was performed to determine factor XIII-A mRNA levels in aortic and cardiac tissue. Factor XIII-A transcripts were assayed in human umbilical blood haemopoietic cell lineages.


Selectivity of Pf4-Cre and Cd11b-Cre mediated deletion was confirmed in liver and spleen. A 40% decrease in factor XIII-A plasma activity was observed in Cd11b mice, whereas plasma activity was decreased by 85% and absent in platelets from Pf4 mice. By contrast, plasma factor XIII-A was normal in Mpl mice. Cd11b mice showed no reduction in factor XIII-A mRNA in cardiac tissue and a 54·6% reduction in aorta. A major decrease in factor XIII-A mRNA was observed in the aorta (91·6%) and heart (99·2%) of Pf4 mice, but there was no change in expression in either tissue from Mpl mice. In a human stem-cell study, factor XIII-A mRNA transcription increased as common myeloid progenitors committed to become granulocyte-macrophage progenitors and as megakaryocyte-erythroid progenitors differentiated to both megakaryocytes and erythroblasts.


These results raise the possibility that a unique Pf4-dependent, Mpl-independent progenitor cell is the major source of the plasma pool. These findings might have implications for the management of factor XIII-A deficiency states.


British Heart Foundation.

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