Spats1-KO Mouse

Spats1, also known as Dishevelled-DEP domain Interacting Protein (DDIP), is a testis-specific protein that has been implicated in spermatogenesis [3,5]. It contains a long serine stretch and a probable bipartite nuclear localization signal. Some reports suggest a link to human pathologies like male infertility and testicular cancer, and it may be involved in the Wnt signaling pathway [1,5]. Genetic models, such as gene knockout mouse models, are valuable for studying its function.

A Spats1 loss-of-function mouse model generated using CRISPR/Cas9 technology showed no overt phenotype, with both male and female mice being fertile. There were no differences in testicular content, histology, sperm concentration, motility, or morphology between wild-type and knockout mice. Also, no changes were detected in the expression levels of typical Wnt pathway-target genes in mutant individuals [1]. In the Chinese soft-shelled turtle, Spats1 is a male-specific expressed gene mainly regulated by 17α-methyltestosterone (MT) and is closely linked to spermatogenesis and release. Its mRNA is highly expressed in the testes and specifically expressed in germ cells [2]. In rats, Spats1 is first expressed in the embryo at 17.5 days post-coitum, and its expression is highest during meiosis of the first spermatogenic wave, suggesting a role in the initiation of the first spermatogenic wave and the first male meiotic division [3]. Bioinformatics analysis identified Spats1 as a hub gene for spermatogenesis, and its expression was examined in testicular germ cell tumors and lipopolysaccharide-induced acute orchitis mice [4].

In conclusion, while Spats1 alteration might be a risk factor for male testicular health, studies using gene knockout mouse models have shown that this gene is not individually essential for male fertility and spermatogenesis in mice. Its role in spermatogenesis and potential association with male-related pathologies in other species, as seen in turtles, rats, and through bioinformatics analysis in humans, indicate its importance in understanding testicular biology and male-related diseases.

References:

1. Capoano, Carlos A, Ortiz-Laquintana, Luis Adrián, Rodríguez-Casuriaga, Rosana, Benavente, Ricardo, Geisinger, Adriana. 2021. SPATS1 (spermatogenesis-associated, serine-rich 1) is not essential for spermatogenesis and fertility in mouse. In PloS one, 16, e0251028. doi:10.1371/journal.pone.0251028. https://pubmed.ncbi.nlm.nih.gov/33945571/

2. Lei, Luo, Zhu, Junxian, Chen, Chen, Li, Wei, Zhu, Xinping. 2022. Expression and Characterization of the Spats1 Gene and Its Response to E2/MT Treatment in the Chinese Soft-Shelled Turtle (Pelodiscus sinensis). In Animals : an open access journal from MDPI, 12, . doi:10.3390/ani12141858. https://pubmed.ncbi.nlm.nih.gov/35883403/

3. Capoano, Carlos A, Wettstein, Rodolfo, Kun, Alejandra, Geisinger, Adriana. 2009. Spats 1 (Srsp1) is differentially expressed during testis development of the rat. In Gene expression patterns : GEP, 10, 1-8. doi:10.1016/j.gep.2009.11.006. https://pubmed.ncbi.nlm.nih.gov/19948251/

4. Liu, Shuang, Bian, Yan-Chao, Wang, Wan-Lun, Xiao, Rui, Zhang, Chuan-Ling. 2023. Identification of hub genes associated with spermatogenesis by bioinformatics analysis. In Scientific reports, 13, 18435. doi:10.1038/s41598-023-45620-3. https://pubmed.ncbi.nlm.nih.gov/37891374/

5. Zhang, Haiwei, Zhang, Hui, Zhang, Yanquan, Guo, Qinglong, Chang, Zhijie. 2010. Dishevelled-DEP domain interacting protein (DDIP) inhibits Wnt signaling by promoting TCF4 degradation and disrupting the TCF4/beta-catenin complex. In Cellular signalling, 22, 1753-60. doi:10.1016/j.cellsig.2010.06.016. https://pubmed.ncbi.nlm.nih.gov/20603214/