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Published on: August 15, 2019
Mutation in beta1-tubulin correlates with macrothrombocytopenia in Cavalier King Charles Spaniels
B Davis1, M Toivio-Kinnucan, S Schuller
1Department of Pathobiology, Auburn University, AL 36849-5519, USA.
Insights
A gene mutation in beta1-tubulin causes macrothrombocytopenia in Cavalier King Charles Spaniels. This finding clarifies the mechanism of platelet production and aids in diagnosing inherited thrombocytopenia.
Area of Science:
- Canine genetics
- Hematology
- Molecular biology
Background:
- Cavalier King Charles Spaniels (CKCS) exhibit a high incidence of inherited macrothrombocytopenia.
- This condition affects platelet size and number, impacting canine health.
Purpose of the Study:
- To investigate the correlation between a specific beta1-tubulin gene mutation and macrothrombocytopenia in CKCS.
- To elucidate the underlying molecular mechanisms of altered platelet production.
Main Methods:
- Blood samples were collected from CKCS and control dogs.
- Polymerase chain reaction (PCR) assays identified beta1-tubulin mutations.
- Platelet counts, mean platelet volume (MPV), electron microscopy, and immunofluorescence were used for analysis.
Main Results:
- A mutation in the beta1-tubulin gene was significantly correlated with macrothrombocytopenia in CKCS.
- Microscopic analysis indicated unstable and reduced platelet microtubules, suggesting impaired proplatelet formation.
Conclusions:
- Inherited macrothrombocytopenia in CKCS is linked to a beta1-tubulin mutation.
- This mutation destabilizes alpha-beta tubulin dimers, affecting megakaryocyte proplatelet formation.
- Findings aid in differentiating inherited from acquired thrombocytopenia and offer insights into platelet production and associated cardiac conditions.
Background:
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.
Hypothesis:
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.
Animals:
Blood samples were obtained from CKCS and non-CKCS dogs.
Methods:
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.
Results:
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.
Conclusions And Clinical Importance:
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.
