TUBB1, Tubulin, Beta 1 Class VI, encodes a member of the β-tubulin protein family. It is a major component of microtubules abundant in megakaryocytes, playing crucial roles in processes like proplatelet formation and platelet shape maintenance. Microtubules are important for normal platelet morphology, and TUBB1 also seems to be involved in DNA damage response, thyroid development and migration, and thyroid hormone secretion [1,2].

In a study on a family with thrombocytopenia and myeloid malignancy, a novel TUBB1 variant (T149P) was identified. Variant TUBB1 disrupted normal microtubule assembly and impaired proplatelet formation in vitro. DNA damage response was severely attenuated by loss of TUBB1, and apoptosis after DNA damage was diminished in TUBB1-deficient cells, suggesting genome instability in affected individuals [1]. In another study, Tubb1 knockout in mice disrupted microtubule integrity in the thyroid, impairing thyroid migration and thyroid hormone secretion. TUBB1 mutations in humans also caused macroplatelets and hyperaggregation of platelets [2].

In conclusion, TUBB1 is essential for microtubule-related functions in platelets and the thyroid. Gene knockout models in mice have revealed its role in platelet formation, DNA damage response, and thyroid development. Understanding TUBB1 functions through these models helps in comprehending the mechanisms of related diseases such as inherited thrombocytopenia and thyroid dysgenesis.

References:

1. Matsumura, Takayoshi, Nakamura-Ishizu, Ayako, Takaoka, Kensuke, Osato, Motomi, Suda, Toshio. 2019. TUBB1 dysfunction in inherited thrombocytopenia causes genome instability. In British journal of haematology, 185, 888-902. doi:10.1111/bjh.15835. https://pubmed.ncbi.nlm.nih.gov/30854628/

2. Stoupa, Athanasia, Adam, Frédéric, Kariyawasam, Dulanjalee, Polak, Michel, Carré, Aurore. . TUBB1 mutations cause thyroid dysgenesis associated with abnormal platelet physiology. In EMBO molecular medicine, 10, . doi:10.15252/emmm.201809569. https://pubmed.ncbi.nlm.nih.gov/30446499/