Ccdc136-KO Mouse

Ccdc136, or coiled-coil domain containing 136, is a gene with diverse functions. It has been implicated in multiple biological processes and diseases. In the context of male reproduction, it is crucial for spermatogenesis, specifically acrosome formation and fertilization [1]. In zebrafish, it plays a role in dorsal-ventral axial patterning by antagonizing the Wnt/β-catenin signaling pathway [4]. Additionally, it has been associated with reading and language phenotypes [2,3,5,6].

In mouse models, Ccdc136-knockout (KO) males were infertile due to a severe defect in acrosome formation. The expression levels of proteins involved in acrosome formation were significantly downregulated in the testes of Ccdc136(-/-) mice compared to wild-type mice. Also, in vitro fertilization assay showed that anti-CCDC136 antibody could inhibit fertilization, demonstrating its essential role in fertilization [1]. In zebrafish, loss-and gain-of-function experiments showed that Ccdc136b (an ortholog) is a crucial negative regulator of the Wnt/β-catenin signaling pathway, and its morphants display strongly dorsalized phenotypes [4].

In conclusion, Ccdc136 is essential for acrosome formation and fertilization in mice, and for dorsal-ventral axial patterning in zebrafish. The gene knockout mouse models have been instrumental in revealing its role in male infertility. Additionally, its association with reading and language phenotypes indicates its potential importance in neurodevelopmental aspects, though further research is needed to fully understand these functions [1,2,3,4,5,6].

References:

1. Geng, Qiang, Ni, Liwei, Ouyang, Bin, Zhao, Yu, Guo, Jun. 2016. A Novel Testis-Specific Gene, Ccdc136, Is Required for Acrosome Formation and Fertilization in Mice. In Reproductive sciences (Thousand Oaks, Calif.), 23, 1387-96. doi:10.1177/1933719116641762. https://pubmed.ncbi.nlm.nih.gov/27076447/

2. Adams, Andrew K, Smith, Shelley D, Truong, Dongnhu T, Pennington, Bruce F, Gruen, Jeffrey R. 2017. Enrichment of putatively damaging rare variants in the DYX2 locus and the reading-related genes CCDC136 and FLNC. In Human genetics, 136, 1395-1405. doi:10.1007/s00439-017-1838-z. https://pubmed.ncbi.nlm.nih.gov/28866788/

3. Gialluisi, Alessandro, Guadalupe, Tulio, Francks, Clyde, Fisher, Simon E. 2016. Neuroimaging genetic analyses of novel candidate genes associated with reading and language. In Brain and language, 172, 9-15. doi:10.1016/j.bandl.2016.07.002. https://pubmed.ncbi.nlm.nih.gov/27476042/

4. Wei, Shi, Shang, Hanqiao, Cao, Yu, Wang, Qiang. 2016. The coiled-coil domain containing protein Ccdc136b antagonizes maternal Wnt/β-catenin activity during zebrafish dorsoventral axial patterning. In Journal of genetics and genomics = Yi chuan xue bao, 43, 431-8. doi:10.1016/j.jgg.2016.05.003. https://pubmed.ncbi.nlm.nih.gov/27477027/

5. Gialluisi, A, Newbury, D F, Wilcutt, E G, Francks, C, Fisher, S E. 2014. Genome-wide screening for DNA variants associated with reading and language traits. In Genes, brain, and behavior, 13, 686-701. doi:10.1111/gbb.12158. https://pubmed.ncbi.nlm.nih.gov/25065397/

6. Unger, Nina, Heim, Stefan, Hilger, Dominique I, Amunts, Katrin, Mühleisen, Thomas W. 2021. Identification of Phonology-Related Genes and Functional Characterization of Broca's and Wernicke's Regions in Language and Learning Disorders. In Frontiers in neuroscience, 15, 680762. doi:10.3389/fnins.2021.680762. https://pubmed.ncbi.nlm.nih.gov/34539327/