Mutation in beta1-tubulin correlates with macrothrombocytopenia in Cavalier King Charles Spaniels.

Davis, B; Toivio-Kinnucan, M; Schuller, Simone; Boudreaux, M K (2008). Mutation in beta1-tubulin correlates with macrothrombocytopenia in Cavalier King Charles Spaniels. Journal of veterinary internal medicine, 22(3), pp. 540-545. Wiley-Blackwell 10.1111/j.1939-1676.2008.0085.x

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > Small Animal Clinic
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > Small Animal Clinic > Small Animal Clinic, Internal Medicine

UniBE Contributor:

Schuller, Simone

Subjects:

600 Technology > 630 Agriculture
600 Technology > 610 Medicine & health

ISSN:

0891-6640

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Simone Schuller

Date Deposited:

10 Oct 2014 10:58

Last Modified:

10 Oct 2014 10:58

Publisher DOI:

10.1111/j.1939-1676.2008.0085.x

PubMed ID:

18466252

URI:

https://boris.unibe.ch/id/eprint/59115

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