TUBB4B is essential for the expansion of differentiating spermatogonia

Microtubules, polymers of αβ-tubulin heterodimers, are essential for various cellular processes. The incorporation of different tubulin isotypes, each encoded by distinct genes, is proposed to contribute to the functional diversity observed in microtubules. However, the functional roles of each tubulin isotype are not completely understood. In this study, we investigated the role of the β4B-tubulin isotype (Tubb4b) in spermatogenesis, utilizing a Tubb4b knockout mouse model. We showed that β4B-tubulin is expressed in the germ cells throughout spermatogenesis. β4B-tubulin was localized to cytoplasmic microtubules, mitotic spindles, manchette, and axonemes of sperm flagella. We found that the absence of β4B-tubulin resulted in male infertility and failure to produce sperm cells. Our findings demonstrate that a lack of β4B-tubulin leads to defects in the initial stages of spermatogenesis. Specifically, β4B-tubulin is needed for the expansion of differentiating spermatogonia, which is essential for the subsequent progression of spermatogenesis.