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

**Authors:** Tao Li, Wei Li, Cheng Zheng, Jannette M. Dufour, William H. Walker, Shuiqiao Yuan, Zhibing Zhang

PMC · DOI: 10.3390/cells14110783 · 2025-05-26

## TL;DR

This study shows that SPAG6L, a protein involved in cytoskeleton function, is not essential for Sertoli cell function in mouse testes.

## Contribution

The study reveals that SPAG6L is not required for Sertoli cell function despite its role in cytoskeleton modulation.

## Key findings

- Sertoli cell-specific Spag6l knockout mice showed no reduction in male fertility.
- Testis size, sperm count, and motility were normal in mutant mice.
- Sertoli cell number and blood-testis barrier function remained unaffected.

## Abstract

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 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, 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 Spag6l does not affect Sertoli cell function during the first 6 months of life.

## Linked entities

- **Genes:** SPAG6 (sperm associated antigen 6) [NCBI Gene 9576], Spag6l (sperm associated antigen 6-like) [NCBI Gene 50525], Plekha5 (pleckstrin homology domain containing, family A member 5) [NCBI Gene 109135]
- **Proteins:** SPAG6 (sperm associated antigen 6), Spag6l (sperm associated antigen 6-like), SPAG6 (sperm associated antigen 6)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Spag6l (sperm associated antigen 6-like) [NCBI Gene 50525] {aka PF16, Spag6, Spag6l1}, Amh (anti-Mullerian hormone) [NCBI Gene 11705] {aka MIS}, Spag6 (sperm associated antigen 6) [NCBI Gene 381350] {aka Gm13334, Spag6l}
- **Species:** Chlamydomonas (genus) [taxon 3052], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12153848/full.md

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Source: https://tomesphere.com/paper/PMC12153848