Molecular and genetic basis for thrombasthenic thrombopathia in otterhounds.
OBJECTIVE
To determine the molecular and genetic basis for thrombasthenic thrombopathia in Otterhounds and establish whether the defect would be best classified as type-I Glanzmann's thrombasthenia.


METHODS
57 dogs, including 13 affected Otterhounds, 23 carrier Otterhounds, 17 unaffected Otterhounds, and 4 clinically normal unrelated dogs of other breeds.


METHODS
Functional (platelet aggregation, clot retraction, buccal mucosa bleeding time) and biochemical (electrophoresis, flow cytometry, fibrinogen content) analyses were conducted. In addition, first-strand cDNA synthesis from platelet total RNA was performed. Exons of the genes encoding for glycoproteins (GP) IIb and IIIa were amplified in overlapping fashion. The resulting products were excised from agarose gels and sequenced. The sequences obtained were compared with known cDNA sequences for canine GPIIb and GPIIIa.


RESULTS
A single nucleotide change at position G1193 (1100) was detected in exon 12 of the gene encoding for platelet GPIIb in 2 affected Otterhounds. Carrier Otterhounds were heterozygous at this position, and 2 unaffected Otterhounds were unchanged. This nucleotide change would result in substitution of histidine for aspartic acid at position 398 (367) within the third calcium-binding domain of GPIIb.


CONCLUSIONS
These studies suggest that thrombasthenic thrombopathia of Otterhounds is homologous phenotypically and has a similar molecular basis to type-I Glanzmann's thrombasthenia in humans.
Boudreaux
M K
MK
Department of Pathobiology, College of Veterinary Medicine, Auburn University, AL 36849-5519, USA.
Catalfamo
J L
JL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002353:Carrier State; D003018:Clot Retraction; D018076:DNA, Complementary / Q000235:genetics; D004283:Dog Diseases / Q000097:blood / Q000235:genetics*; D004285:Dogs; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D039421:Integrin alpha2; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009061:Mouth Mucosa / Q000473:pathology; D010375:Pedigree; D010974:Platelet Aggregation / Q000235:genetics; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D012689:Sequence Homology, Nucleic Acid; D013915:Thrombasthenia / Q000097:blood / Q000235:genetics / Q000662:veterinary*
D018955:CD36 Antigens; D018076:DNA, Complementary; C056564:ITGA2B protein, human; D039421:Integrin alpha2; D008562:Membrane Glycoproteins; D012313:RNA; D005340:Fibrinogen