Characterization of a Feline Model of Factor XII Deficiency: The In Vivo Role of FXII in Vascular Injury and Inflammatory Responses

Coagulation factor XII (FXII) assists in thrombus formation and may be important in cardiovascular and inflammatory mediated diseases. We have identified a naturally occurring mutation in the feline FXII gene that encodes a catalytically inactive mutant protein. We sequenced the genomic loci encoding factor XII in wild type cats and analyzed mRNA sequences encoding FXII in wild type and FXII deficient mutants. The feline Factor XII gene comprises fourteen exons ranging in size from 57 to 222 base pairs and spanning 11 kilobases on chromosome A1. The wild type feline FXII gene encodes a transcript that is 1833 base pair long and contains an open reading frame encoding a protein of 610 amino acids. Analysis of RNA from factor XII wild type and mutant cats revealed one single base deletion in exon 11 of the FXII coding gene in the FXII deficient cats. The deletion caused a frame-shift at L (LeuCys) resulting in a nonsense mutation, a premature stop codon, and a truncated factor XII protein of 561 amino acids. The mutant FXII protein lacks the catalytic triad domain located in the C-terminus between His and