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Thromb Haemost 1998; 79(02): 317-322
DOI: 10.1055/s-0037-1614984
Letters to the Editor
Schattauer GmbH

The Canine Factor VIII cDNA and 5’ Flanking Sequence

Cherie Cameron
1   From the Department of Pathology, Queen’s University, Richardson Laboratory, Kingston, Ontario, Canada
,
Colleen Notley
1   From the Department of Pathology, Queen’s University, Richardson Laboratory, Kingston, Ontario, Canada
,
Susan Hoyle
1   From the Department of Pathology, Queen’s University, Richardson Laboratory, Kingston, Ontario, Canada
,
Leslie McGlynn
1   From the Department of Pathology, Queen’s University, Richardson Laboratory, Kingston, Ontario, Canada
,
Christine Hough
1   From the Department of Pathology, Queen’s University, Richardson Laboratory, Kingston, Ontario, Canada
,
Seiki Kamisue
1   From the Department of Pathology, Queen’s University, Richardson Laboratory, Kingston, Ontario, Canada
,
Alan Giles
1   From the Department of Pathology, Queen’s University, Richardson Laboratory, Kingston, Ontario, Canada
,
David Lillicrap
1   From the Department of Pathology, Queen’s University, Richardson Laboratory, Kingston, Ontario, Canada
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Publikationsverlauf

Received 08. April 1997

Accepted after resubmission 10. September 1997

Publikationsdatum:
08. Dezember 2017 (online)

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Summary

Factor VIII is a trace plasma glycoprotein involved as a cofactor in the activation of factor X by factor IXa. Inherited deficiency of factor VIII results in the X-linked bleeding disorder hemophilia A which has been documented in humans, horses, sheep and dogs. In this report, the putative proximal promoter, 5’ untranslated region, complete coding sequence and 3’ untranslated region of the canine factor VIII gene have been characterized. When compared to the human gene, the 5’ flanking region shows conservation of transcription factor binding sites in the 5’ untranslated region. Alignment of the amino acid sequence with that of the previously reported human, mouse and pig proteins demonstrates sequence identity of between 77 and 92% for the A1, A2, A3, C1 and C2 domains but an identity of only between 44 and 62% for the central B domain. The three thrombin cleavage sites are conserved in the canine sequence as are the protein C cleavage sites and the von Wille-brand factor binding region. In addition, all six tyrosine residues that are known to undergo sulfation in the human protein are conserved in the dog. The 3’ untranslated region of the canine gene extends 1.5 kilo-bases. The initial 700 basepairs of this sequence are highly GC rich and the sequence terminates with 2 alternative potential polyadenylation sites. The knowledge of this sequence, in combination with a well described canine model of hemophilia A, provides the necessary starting point for studies addressing the long-term evaluation of factor VIII gene therapy using a homologous transgene.

 

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