Meinkoth J H, Meyers K M
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, College of Veterinary Medicine, Washington State University, Pullman 99164-6520, USA.
Am J Vet Res. 1995 Dec;56(12):1577-85.
To characterize the cellular basis of the plasma von Willebrand factor (vWf) deficiency in Doberman Pinschers with type-1 von Willebrand's disease (vWd).
Five Doberman Pinschers with type-I vWd and 5 clinically normal dogs used as controls.
Vascular endothelial cell cultures were used to measure constitutive vWf release, thrombin-stimulated vWf release, baseline intracellular vWf concentration, and vWf mRNA expression.
Cells cultured from vWd-affected dogs were morphologically indistinguishable from cells cultured from control dogs, but had reductions in constitutive vWf release (6.5-fold) and vWf mRNA content (fivefold) that correlated to the reduction in plasma vWf concentration (sixfold) in these dogs. The 9.0-kb, canine vWf message was identified, using a polymerase chain reaction-amplified segment of the canine vWf gene and was similar in size to the human vWf message. The vWd cells also had reductions in baseline intracellular vWf concentration (15.6-fold) and thrombin-stimulated vWf release (14.5-fold). Additionally, it was observed that normal canine endothelial cells from different anatomic locations were heterogeneous with respect to vWf expression.
These findings suggest that the plasma vWf deficit in dogs with type-I vWd results from decreased endothelial cell production of vWf resulting from either decreased transcription of the vWf gene or abnormalities in mRNA processing/stability. This is similar to findings in human beings with type-I vWd.
明确患有1型血管性血友病（vWd）的杜宾犬血浆血管性血友病因子（vWf）缺乏的细胞基础。
5只患有I型vWd的杜宾犬和5只临床正常的犬作为对照。
采用血管内皮细胞培养来测量组成型vWf释放、凝血酶刺激的vWf释放、基线细胞内vWf浓度和vWf mRNA表达。
从受vWd影响的犬培养的细胞在形态上与从对照犬培养的细胞无法区分，但组成型vWf释放（6.5倍）和vWf mRNA含量（5倍）降低，这与这些犬血浆vWf浓度降低（6倍）相关。使用犬vWf基因的聚合酶链反应扩增片段鉴定出9.0 kb的犬vWf信息，其大小与人类vWf信息相似。vWd细胞的基线细胞内vWf浓度（15.6倍）和凝血酶刺激的vWf释放（14.5倍）也降低。此外，观察到来自不同解剖位置的正常犬内皮细胞在vWf表达方面存在异质性。
这些发现表明，I型vWd犬的血浆vWf缺乏是由于vWf基因转录减少或mRNA加工/稳定性异常导致内皮细胞产生vWf减少所致。这与I型vWd人类的发现相似。
