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Publication : Spastin is an essential regulator of male meiosis, acrosome formation, manchette structure and nuclear integrity.

First Author  Cheers SR Year  2023
Journal  Development Volume  150
Issue  6 PubMed ID  36971361
Mgi Jnum  J:334562 Mgi Id  MGI:7451256
Doi  10.1242/dev.201183 Citation  Cheers SR, et al. (2023) Spastin is an essential regulator of male meiosis, acrosome formation, manchette structure and nuclear integrity. Development 150(6):dev201183
abstractText  The development and function of male gametes is dependent on a dynamic microtubule network, yet how this is regulated remains poorly understood. We have recently shown that microtubule severing, via the action of the meiotic AAA ATPase protein clade, plays a crucial role in this process. Here, we sought to elucidate the roles of spastin, an as-yet-unexplored member of this clade in spermatogenesis. Using a SpastKO/KO mouse model, we reveal that spastin loss resulted in a complete loss of functional germ cells. Spastin plays a crucial role in the assembly and function of the male meiotic spindle. Consistent with meiotic failure, round spermatid nuclei were enlarged, indicating aneuploidy, but were still able to enter spermiogenesis. During spermiogenesis, we observed extreme abnormalities in manchette structure, acrosome biogenesis and, commonly, a catastrophic loss of nuclear integrity. This work defines an essential role for spastin in regulating microtubule dynamics during spermatogenesis, and is of potential relevance to individuals carrying spastin variants and to the medically assisted reproductive technology industry.
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