PubMed Health⌕ Search

Biomedical subjects

E Idusogie

Publications and source records attributed to E Idusogie.

3 recordsLinked to original sources

Mice lacking factor VII develop normally but suffer fatal perinatal bleeding.

Blood coagulation in vivo is initiated by factor VII (FVII) binding to its cellular receptor tissue factor (TF). FVII is the only known ligand for TF, so it was expected that FVII-deficient embryos would have a similar phenotype to TF-deficient embryos, which have defective vitello-embryonic circulation and die around 9.5 days of gestation. Surprisingly, we find that FVII-deficient (FVII-/-) embryos developed normally. FVII-/- mice succumbed perinatally because of fatal haemorrhaging from normal blood vessels. At embryonic day 9.5, maternal-fetal transfer of FVII was undetectable and survival of embryos did not depend on TF-FVII-initiated fibrin formation. Thus, the TF-/- embryonic lethal and the FVII-/- survival-phenotypes suggest a role for TF during embryogenesis beyond fibrin formation.

Animals↗

Characterization of a cDNA encoding murine coagulation factor VII.

The cDNA encoding murine coagulation factor VII (mfVII) was isolated and reconstructed from a lambda Zap cDNA library generated from murine liver mRNA. The cDNA contains 1903 nucleotides spanning 15 bases upstream of the 5'-translation initiation codon, an open reading frame of 1338 nucleotides, 550 nucleotides downstream of the first stop codon and a 3' poly(A) tail. The translation product is composed of a 41-amino acid signal/propeptide region followed by a 405-residue mature protein. The latter is highly homologous to that of human, rabbit, bovine, Rhesus monkey, and canine fVII. All protein domains of hfVII are strictly conserved in mfVII.

Amino Acid Sequence↗

Nucleotide structure and characterization of the murine blood coagulation factor VII gene.

The gene encoding murine coagulation factor VII (fVII) has been cloned. Seven introns and eight exons are present, with the introns positioned as splice junctions between the major domain units of the protein. A total of 11,748 bp of the gene was sequenced, and included 1,077 bp of a 5'-flanking region, in which several high probability binding sites for liver transcription factors were present, as well as a CCAAT sequence and possible GC boxes. Primer extension analysis revealed that the major transcription start site was positioned only 9 residues upstream of the ATG initiation codon, thus providing a very short 5'-untranslated region of the gene. The sequence of the CAP site in the murine fVII gene matched exactly the consensus eukaryotic sequence. A total of 1,484 bp of 3'-flanking nucleotides included a probable polyadenylation site (ATTAAA) and an appropriately positioned downstream consensus sequence (AGTGTTTC) for the efficient formation of a 3' terminus of mRNA. These results indicate that all elements are present for liver-based transcription of the gene for murine factor VII. The sequence and restriction endonuclease map of this gene will facilitate construction of fVII deficient mice and mice containing mutant fVII genes.

Amino Acid Sequence↗