Sox8 is a transcription factor belonging to the Sox family of high-mobility-group domain containing proteins, closely related to Sox9 and Sox10. It is expressed in multiple tissues derived from ectoderm, endoderm, and mesoderm during prenatal development and is involved in organogenesis and differentiation processes. It functions in important cells like Sertoli cells, glial cells, satellite cells, and chondrocytes [1].

In the Chinese soft-shelled turtle Pelodiscus sinensis, knockdown of SOX8 led to complete feminization of ZZ individuals, down-regulation of testicular marker DMRT1, and up-regulation of ovarian regulator FOXL2, indicating its essential role in male sexual differentiation [2]. In mouse spermatogonia, the long non-coding RNA Mrhl regulates Sox8 in a p68-dependant manner, and down-regulation of Mrhl leads to meiotic commitment of spermatogonial cells in a Sox8-dependant way [3]. In the cuprizone model, Sox8-/-mice showed reduced motor performance, weight, oligodendrocyte precursor cell proliferation, and mature oligodendrocyte numbers, along with a delay in remyelination, demonstrating its importance in remyelination processes [4].

In conclusion, Sox8 is crucial for male sexual differentiation in reptiles, sex maintenance and fertility in adult mice, and remyelination in a disease model. The use of gene knockout (KO) models in these studies has significantly contributed to understanding the role of Sox8 in these biological processes, providing insights into potential disease mechanisms related to sexual development and nervous system diseases.

References:

1. González Alvarado, María Nazareth, Aprato, Jessica. 2025. Sox8: a multifaceted transcription factor in development and disease. In Biology open, 14, . doi:10.1242/bio.061840. https://pubmed.ncbi.nlm.nih.gov/39936824/

2. Yang, Bangsai, Sun, Wei, Jin, Lin, Ge, Chutian, Xiao, Ling. . SOX8 is essential for male sexual differentiation in the Chinese soft-shelled turtle Pelodiscus sinensis‡. In Biology of reproduction, 108, 988-996. doi:10.1093/biolre/ioad033. https://pubmed.ncbi.nlm.nih.gov/36943308/

3. Kayyar, Bhavana, Ravikkumar, Anjhana C, Bhaduri, Utsa, Rao, M R S. 2022. Regulation of Sox8 through lncRNA Mrhl-Mediated Chromatin Looping in Mouse Spermatogonia. In Molecular and cellular biology, 42, e0047521. doi:10.1128/mcb.00475-21. https://pubmed.ncbi.nlm.nih.gov/35412350/

4. Freudenstein, David, Lippert, Magdalena, Popp, Janina Sophie, Linker, Ralf A, González Alvarado, María Nazareth. 2023. Endogenous Sox8 is a critical factor for timely remyelination and oligodendroglial cell repletion in the cuprizone model. In Scientific reports, 13, 22272. doi:10.1038/s41598-023-49476-5. https://pubmed.ncbi.nlm.nih.gov/38097655/