(10) Function of the TEX25 gene family in mouse spermatogenesis 

Fang Yang¹, Maya Kennedy¹, Ankit Jaiswal¹, Adrian Leu¹, and P. Jeremy Wang¹

¹Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, US.


Abstract Text:  
 Spermatogenesis consists of several key developmental stages, including meiosis and spermiogenesis. During meiosis, meiotic recombination nodules are formed on programmed double strand DNA breaks (DSBs). About 10% of DSBs develop into crossovers. Each pair of homologous chromosomes has at least one crossover including XY chromosomes. On one hand, crossovers are essential for faithful chromosome segregation. On the other hand, crossovers increase genetic diversity in gametes and thus in offspring. Our previous study shows that TEX11 is a component of meiotic nodules. Deletion of TEX11 partially affects homologous chromosome synapsis and reduces crossover number, which leads to male sterile and female subfertility. To investigate the mechanism of TEX11 in meiosis, we performed immunoprecipitation-mass spectrometry screen with Flag tagged TEX11 testes to systematically identify TEX11-associated proteins. Two unknown proteins from this screen belong to a testis-specific gene family that we named Tex25. There are four members: Tex25a-d. Tex25a, Tex25b, and Tex25c are located in a gene cluster on the X chromosome, and Tex25d is a retrogene with only one exon on Chromosome 15. We deleted the three X-linked Tex25 genes in mice using the CRISPR/Cas9 genome-editing approach. We found that the Tex25 triple KO males have slightly reduced testis weight and sperm count. In closer analysis, we found increased sex chromosome asynapsis in Tex25 triple KO pachytene spermatocytes and increased apoptotic germ cells in stage XII tubules. However, sperm motility tests and mating tests did not show significant difference between WT and Tex25 triple KO males. At the same time, we deleted the autosomal paralogue Tex25d. Tex25d-deficient mice are fertile with normal testis weight and sperm count. It is possible that there is functional redundancy among TEX25 family members. In our ongoing study, we are generating Tex25 quadruple KO mice to examine the function of the entire Tex25 family in mouse spermatogenesis.