Protein C is a precursor to a
serine protease present in the plasma that plays an important physiological role in the regulation of blood coagulation. Mutations in the human
protein C gene have been linked to some cases of Morbus
Perthes disease, a thrombophilic condition that results in aseptic
necrosis of the femur head and neck. We have cloned the canine
protein C gene to investigate whether Morbus
Perthes disease in dogs is also caused by mutations within this gene. A genomic lambdaFIXII clone was isolated, and 11, 420 bp of DNA sequence were determined containing the complete
protein C gene (Acc No. AJ001979). As in humans, the gene consists of nine exons with the translation
start codon located in the second exon. The 1.7-kb
mRNA contains a 1368-bp open reading frame coding for 456
amino acids. With the genomic
protein C clone as a probe in a FISH experiment, the canine
protein C gene was assigned to Chromosome (Chr) 19q21-q22. To search for possible mutations, we amplified genomic
DNA from one healthy and 15 clinically and pathohistologically confirmed Morbus Perthes patients. Sequence analysis did not reveal any
amino acid differences between the affected dogs and the normal control. Several
nucleotide polymorphisms were detected, which however, did not result in an
amino acid exchange. From these data we conclude that in contrast to human, canine Morbus
Perthes disease is most likely not caused by mutations within the
protein C gene.