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, which is localized in the central apparatus of the motile cilia and is essential for ciliary motility. Even though the amino acid sequences of the two SPAG6 proteins are highly similar, the two proteins have different biological expression patterns in vivo. No major phenotypes were discovered in the global <i>Spag6</i> knockout mice. However, the global <i>Spag6l</i> 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 <i>Spag6l</i> mice were crossed with <i>Amh-Cre</i> transgenic mice to inactivate the <i>Spag6l</i> gene specifically in Sertoli cells. Surprisingly, the fertility of the homozygous mutant males was not reduced. The testis size and sperm number and motility showed no significant difference to those of 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 the inactivation of only <i>Spag6l</i> does not affect Sertoli cell function during the first 6 months of life.