Temporal expression of alternatively spliced forms of tissue factor pathway inhibitor in mice

Background: Mouse tissue factor pathway inhibitor (TFPI) is produced in three alternatively spliced isoforms that differ in domain structure and mechanism for cell surface binding. Tissue expression of TFPI isoforms in mice was characterized as an initial step for identification of their physiological functions. Methods and Results: Sequence homology demonstrates that TFPI alpha existed over 430 Ma while TFPI beta and TFPI gamma evolved more recently. In situ hybridization studies of heart and lung did not reveal any cells exclusively expressing a single isoform. Although our previous studies have demonstrated that TFPI alpha mRNA is more prevalent than TFPI beta or TFPI gamma mRNA in mouse tissues, western blot studies demonstrated that TFPI beta is the primary protein isoform produced in adult tissues, while TFPI alpha is expressed during embryonic development and in placenta. Consistent with TFPI beta as the primary isoform produced within adult vascular beds, the TFPI isoform in mouse plasma migrates like TFPI beta in SDS-PAGE and mice have a much smaller heparin-releasable pool of plasma TFPI alpha than humans. Conclusions: The data demonstrate that alternatively spliced isoforms of TFPI are temporally expressed in mouse tissues at the level of protein production. TFPI alpha and TFPI beta are produced in embryonic tissues and in placenta while adult tissues produce almost exclusively TFPI beta.