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.


RESULTS
Sequence homology demonstrates that TFPIalpha existed over 430 Ma while TFPIbeta and TFPIgamma 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 TFPIalpha mRNA is more prevalent than TFPIbeta or TFPIgamma mRNA in mouse tissues, western blot studies demonstrated that TFPIbeta is the primary protein isoform produced in adult tissues, while TFPIalpha is expressed during embryonic development and in placenta. Consistent with TFPIbeta as the primary isoform produced within adult vascular beds, the TFPI isoform in mouse plasma migrates like TFPIbeta in SDS-PAGE and mice have a much smaller heparin-releasable pool of plasma TFPIalpha than humans.


CONCLUSIONS
The data demonstrate that alternatively spliced isoforms of TFPI are temporally expressed in mouse tissues at the level of protein production. TFPIalpha and TFPIbeta are produced in embryonic tissues and in placenta while adult tissues produce almost exclusively TFPIbeta.
Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53201-2178, USA.
S A
SA
Maroney
J P
JP
Ferrel
S
S
Pan
T A
TA
White
R D
RD
Simari
J H
JH
McVey
A E
AE
Mast
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D017124:Conserved Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017403:In Situ Hybridization; D008074:Lipoproteins / Q000737:chemistry / Q000235:genetics*; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D008074:Lipoproteins; D012333:RNA, Messenger; C051928:lipoprotein-associated coagulation inhibitor