Spag1-KO Mouse

Spag1, or sperm-associated antigen 1, is a multidomain protein. It is essential for the assembly of axonemal dynein arms in cilia, a process crucial for the function of motile cells. It interacts with multiple dynein axonemal assembly factors (DNAAFs), dynein chains and components of the R2TP complex, and is necessary for scaffolding R2TP-like complexes that facilitate the folding and binding of dynein heavy chains (DHCs) to the dynein intermediate chain (DIC) complex [2,4,6]. Mutations in Spag1 result in primary ciliary dyskinesia (PCD), a disorder characterized by chronic oto-sino-pulmonary disease, infertility and laterality defects [2,3,7,8].

In acute myeloid leukemia (AML), Spag1 is widely expressed and its high expression is associated with a poor prognosis. RNA interference knockdown tests showed that Spag1 promotes the proliferation and survival of AML cells, regulates the expression of structural maintenance of chromosomes protein 3 (SMC3), and activates the ERK/MAPK signaling pathway. Inhibiting Spag1 also impacts AML cell susceptibility to venetoclax. Bioinformatics and clinical validation further confirmed that Spag1 overexpression may serve as an independent prognostic biomarker and guide treatment choice between hematopoietic stem cell transplantation (HSCT) and chemotherapy in AML patients [1,5]. In porcine immature Sertoli cells, miR-638 targets Spag1 to inhibit cell proliferation, cell cycle, and promote apoptosis, and it indirectly inactivates the PI3K/AKT pathway [9].

In conclusion, Spag1 plays a crucial role in cilia-related biological functions and is associated with PCD. In the context of AML, it affects cell proliferation, survival, and chemotherapy sensitivity, highlighting its potential as a therapeutic target. The study of Spag1 in these disease areas, through methods like RNA interference knockdown (functionally similar to gene knockout in revealing gene function), provides insights into disease mechanisms and potential treatment strategies.