Mouse SPAG6L, a Key Cytoskeleton Modulator Essential for Male Germ Cell Development, Is Not Required for Sertoli Cell Function

Mouse sperm-associated antigen 6-like (SPAG6L) evolved from SPAG6, the mammalian ortholog of Chlamydomonas PF16 that is localized in the central apparatus in the motile cilia and essential for cilia motility. Even though the amino acid sequences of the two SPAG6 proteins are highly similar, the two proteins have different biological activities in vivo. No major phenotypes were discovered in the global Spag6 knockout mice. However, the global Spag6l knockout mice demonstrated multiple phenotypes in tissues with and without cilia. Since SPAG6L decorates microtubules and modulates cytoskeleton function, and Sertoli cells have a well-developed microtubule transport network, the potential function of SPAG6L in Sertoli cells was evaluated. The floxed Spag6l mice were crossed with Amh-Cre transgenic mice to inactivate the Spag6l gene specifically in Sertoli cells. Surprisingly, fertility of the homozygous mutant males was not reduced. The testis size, sperm number and motility were comparable to the control mice. Testicular histology also showed normal spermatogenesis. No significant changes were observed in the number of Sertoli cells and blood-testis barrier function. Our study showed that inactivation of only Spag6l does not affect Sertoli cell function during the first 6 months of life.