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Sequence of the murine factor VIII cDNA

B Elder1, D Lakich, J Gitschier

  • 1Department of Medicine, University of California, San Francisco 94143.

Genomics
|May 1, 1993
PubMed
Summary

Researchers isolated and sequenced the mouse factor VIII gene, finding it functions similarly to human factor VIII in blood clotting but with key structural differences.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Factor VIII is a critical protein in the blood coagulation cascade.
  • Understanding the genetic and protein structure of factor VIII across species aids in comprehending its function and evolution.

Purpose of the Study:

  • To isolate and sequence DNA clones of the mouse homolog of the human factor VIII gene.
  • To compare the structure and identify conserved and divergent regions between mouse and human factor VIII.

Main Methods:

  • DNA cloning and sequencing techniques were employed.
  • Comparative analysis of gene and protein sequences between mouse and human factor VIII.

Main Results:

  • The mouse factor VIII gene is expressed in various tissues, with its mRNA being shorter than human mRNA due to a truncated 3' untranslated region.
  • The mouse factor VIII protein shares 74% amino acid identity with human factor VIII, with high conservation in functionally critical A and C domains.
  • Key functional sites, including thrombin/factor Xa cleavage sites and von Willebrand factor binding residues, are conserved, while B and acidic domains show divergence.

Conclusions:

  • Mouse factor VIII likely operates similarly to human factor VIII in the coagulation cascade.
  • Observed sequence differences, particularly in divergent domains, may indicate functional variations between mouse and human factor VIII.

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