Davis B, Toivio-Kinnucan M, Schuller S, Boudreaux M K
Department of Pathobiology, Auburn University, AL 36849-5519, USA.
J Vet Intern Med. 2008 May-Jun;22(3):540-5. doi: 10.1111/j.1939-1676.2008.0085.x. Epub 2008 May 2.
Cavalier King Charles Spaniels (CKCS) have a high prevalence of inherited macrothrombocytopenia. The purpose of this study was to determine if a mutation in beta1-tubulin correlated with presumptive inherited macrothrombocytopenia.
A mutation in beta1-tubulin results in synthesis of an altered beta1-tubulin monomer. alpha-beta tubulin dimers within microtubule protofilaments are unstable, resulting in altered megakaryocyte proplatelet formation.
Blood samples were obtained from CKCS and non-CKCS dogs.
DNA was used in polymerase chain reaction (PCR) assays to evaluate beta1-tubulin. Platelet numbers and mean platelet volume (MPV) were evaluated for a correlation with the presence or absence of a mutation identified in beta1-tubulin. Platelets obtained from homozygous, heterozygous, and clear CKCS were further evaluated using electron microscopy and immunofluorescence.
A mutation in the gene encoding beta1-tubulin correlated with macrothrombocytopenia in CKCS. Electron microscopy and immunofluorescence studies suggest that platelet microtubules are present but most likely are unstable and decreased in number.
The macrothrombocytopenia of CKCS correlated with a mutation in beta1-tubulin. alpha-beta tubulin dimers within protofilaments most likely are unstable, leading to altered proplatelet formation by megakaryocytes. This information will aid in distinguishing inherited from acquired thrombocytopenia. It also provides insight into the mechanism of platelet production by megakaryocytes, and also may prove useful in understanding heart-related changes in macrothrombocytopenic CKCS with concurrent mitral valve regurgitation.
骑士查理王小猎犬（CKCS）遗传性大血小板减少症的患病率很高。本研究的目的是确定β1 -微管蛋白的突变是否与推定的遗传性大血小板减少症相关。
β1 -微管蛋白的突变导致合成改变的β1 -微管蛋白单体。微管原纤维内的α-β微管蛋白二聚体不稳定，导致巨核细胞前血小板形成改变。
从CKCS和非CKCS犬获取血样。
使用DNA进行聚合酶链反应（PCR）分析以评估β1 -微管蛋白。评估血小板数量和平均血小板体积（MPV）与β1 -微管蛋白中鉴定出的突变的存在与否的相关性。使用电子显微镜和免疫荧光进一步评估从纯合、杂合和野生型CKCS获得的血小板。
编码β1 -微管蛋白的基因中的突变与CKCS中的大血小板减少症相关。电子显微镜和免疫荧光研究表明血小板微管存在，但很可能不稳定且数量减少。
CKCS的大血小板减少症与β1 -微管蛋白的突变相关。原纤维内的α-β微管蛋白二聚体很可能不稳定，导致巨核细胞前血小板形成改变。这些信息将有助于区分遗传性血小板减少症和获得性血小板减少症。它还提供了对巨核细胞产生血小板机制的见解，并且在理解并发二尖瓣反流的大血小板减少症CKCS的心脏相关变化方面可能也有用。
