Knockout of the family with sequence similarity 181, member A (Fam181a) gene does not impair spermatogenesis or male fertility in the mouse
Wasim Shah A , Ranjha Khan
A B , Basit Shah A , Sobia Dil A and Qinghua Shi A B
+ Author Affiliations
- Author Affiliations
A The First Affiliated Hospital of the University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
B Corresponding authors. Email: ranjha@ustc.edu.cn; qshi@ustc.edu.cn
Reproduction, Fertility and Development 33(10) 674-681 https://doi.org/10.1071/RD21150
Submitted: 26 May 2021 Accepted: 16 June 2021 Published: 13 July 2021
Abstract
Family with sequence similarity 181 (Fam181) is a gene family with two paralogues (Fam181a and Fam181b) found among vertebrates. Fam181a exhibits dynamic and stage-specific expression during murine embryo development. Furthermore, searching in the National Center for Biotechnology Information database revealed predominant expression of Fam181a in mouse and human testes, implying that it may have essential roles in spermatogenesis. In this study we investigated the in vivo function of Fam181a in mouse spermatogenesis and fertility by generating Fam181a–/– mice using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) 9 genome editing technology. The resulting Fam181a–/– mice exhibited normal growth and development. In addition, the mice were completely fertile, with no obvious differences in the testis-to-bodyweight ratio, epididymal sperm count or sperm motility compared with wild-type mice. Further examination of testicular and epididymal histology of Fam181a–/– mice found an intact seminiferous tubule structure and the presence of all types of germ cells, from spermatogonia to mature spermatozoa, similar to wild-type littermates. Similarly, analysis of meiotic prophase I progression revealed normal populations of each substage of prophase I in Fam181a+/+ and Fam181a–/– testes, suggesting that this gene is dispensable for male fertility. These negative findings will help avoid research overlap, save time and resources and allow researchers to concentrate on genes that are critical for male fertility and spermatogenesis.
Keywords: Fam181a, fertility, spermatogenesis, testis specific.
References
Abou-Haila, A., and Tulsiani, D. R. (2000). Mammalian sperm acrosome: formation, contents, and function. Arch. Biochem. Biophys. 379, 173–182.| Mammalian sperm acrosome: formation, contents, and function.Crossref | GoogleScholarGoogle Scholar | 10898932PubMed |
Chotiner, J. Y., Leu, N. A., and Wang, P. J. (2020). FLACC1 is testis-specific but dispensable for fertility in mice. Mol. Reprod. Dev. 87, 1199–1201.
| FLACC1 is testis-specific but dispensable for fertility in mice.Crossref | GoogleScholarGoogle Scholar | 33156557PubMed |
Devlin, D. J., Nozawa, K., Ikawa, M., and Matzuk, M. M. (2020). Knockout of family with sequence similarity 170 member A (Fam170a) causes male subfertility, while Fam170b is dispensable in mice. Biol. Reprod. 103, 205–222.
| Knockout of family with sequence similarity 170 member A (Fam170a) causes male subfertility, while Fam170b is dispensable in mice.Crossref | GoogleScholarGoogle Scholar | 32588889PubMed |
Gao, Q., Khan, R., Yu, C., Alsheimer, M., Jiang, X., Ma, H., and Shi, Q. (2020). The testis-specific LINC component SUN3 is essential for sperm head shaping during mouse spermiogenesis. J. Biol. Chem. 295, 6289–6298.
| The testis-specific LINC component SUN3 is essential for sperm head shaping during mouse spermiogenesis.Crossref | GoogleScholarGoogle Scholar | 32156700PubMed |
Greenbaum, M. P., Yan, W., Wu, M.-H., Lin, Y.-N., Agno, J. E., Sharma, M., Braun, R. E., Rajkovic, A., and Matzuk, M. M. (2006). TEX14 is essential for intercellular bridges and fertility in male mice. Proc. Natl Acad. Sci. USA 103, 4982–4987.
| TEX14 is essential for intercellular bridges and fertility in male mice.Crossref | GoogleScholarGoogle Scholar | 16549803PubMed |
Guo, S., Ouyang, S., Wang, X., Liao, A., and Yuan, S. (2020). GOLGA4, a Golgi matrix protein, is dispensable for spermatogenesis and male fertility in mice. Biochem. Biophys. Res. Commun. 529, 642–646.
| GOLGA4, a Golgi matrix protein, is dispensable for spermatogenesis and male fertility in mice.Crossref | GoogleScholarGoogle Scholar | 32736686PubMed |
Hagaman, J. R., Moyer, J. S., Bachman, E. S., Sibony, M., Magyar, P. L., Welch, J. E., Smithies, O., Krege, J. H., and O’Brien, D. A. (1998). Angiotensin-converting enzyme and male fertility. Proc. Natl Acad. Sci. USA 95, 2552–2557.
| Angiotensin-converting enzyme and male fertility.Crossref | GoogleScholarGoogle Scholar | 9482924PubMed |
Holcomb, R. J., Oura, S., Nozawa, K., Kent, K., Yu, Z., Robertson, M. J., Coarfa, C., Matzuk, M. M., Ikawa, M., and Garcia, T. X. (2020). The testis-specific serine proteases PRSS44, PRSS46, and PRSS54 are dispensable for male mouse fertility. Biol. Reprod. 102, 84–91.
| 31403672PubMed |
Huang, X. Y., Guo, X. J., Shen, J., Wang, Y. F., Chen, L., Xie, J., Wang, N. L., Wang, F. Q., Zhao, C., Huo, R., Lin, M., Wang, X., Zhou, Z. M., and Sha, J. H. (2008). Construction of a proteome profile and functional analysis of the proteins involved in the initiation of mouse spermatogenesis. J. Proteome Res. 7, 3435–3446.
| Construction of a proteome profile and functional analysis of the proteins involved in the initiation of mouse spermatogenesis.Crossref | GoogleScholarGoogle Scholar | 18582094PubMed |
Iwamori, N., Zhao, M., Meistrich, M. L., and Matzuk, M. M. (2011). The testis-enriched histone demethylase, KDM4D, regulates methylation of histone H3 lysine 9 during spermatogenesis in the mouse but is dispensable for fertility. Biol. Reprod. 84, 1225–1234.
| The testis-enriched histone demethylase, KDM4D, regulates methylation of histone H3 lysine 9 during spermatogenesis in the mouse but is dispensable for fertility.Crossref | GoogleScholarGoogle Scholar | 21293030PubMed |
Jiang, H., Wang, L., Cui, Y., Xu, Z., Guo, T., Cheng, D., Xu, P., Yu, W., and Shi, Q. (2014). Meiotic chromosome behavior in a human male t(8;15) carrier. J. Genet. Genomics 41, 177–185.
| Meiotic chromosome behavior in a human male t(8;15) carrier.Crossref | GoogleScholarGoogle Scholar | 24656237PubMed |
Jiang, X., Ma, T., Zhang, Y., Zhang, H., Yin, S., Zheng, W., Wang, L., Wang, Z., Khan, M., and Sheikh, S. W. (2015). Specific deletion of Cdh2 in Sertoli cells leads to altered meiotic progression and subfertility of mice. Biol. Reprod. 92, 79.
| Specific deletion of Cdh2 in Sertoli cells leads to altered meiotic progression and subfertility of mice.Crossref | GoogleScholarGoogle Scholar | 25631347PubMed |
Jiang, H., Li, T., Fan, S., Jiang, X., and Shi, Q. (2017). Chromosome behavior and the molecular basis of meiosis. Scientia Sinica Vitae 47, 16–25.
| Chromosome behavior and the molecular basis of meiosis.Crossref | GoogleScholarGoogle Scholar |
Khan, R., Ye, J., Yousaf, A., Shah, W., Aftab, A., Shah, B., Zaman, Q., Zubair, M., Shi, Q., and Jiang, X. (2020). Evolutionarily conserved and testis-specific gene, 4930524B15Rik, is not essential for mouse spermatogenesis and fertility. Mol. Biol. Rep. 47, 5207–5213.
| Evolutionarily conserved and testis-specific gene, 4930524B15Rik, is not essential for mouse spermatogenesis and fertility.Crossref | GoogleScholarGoogle Scholar | 32592116PubMed |
Kumar, S., Stecher, G., and Tamura, K. (2016). MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol. Biol. Evol. 33, 1870–1874.
| MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets.Crossref | GoogleScholarGoogle Scholar | 27004904PubMed |
Lu, Y., Oura, S., Matsumura, T., Oji, A., Sakurai, N., Fujihara, Y., Shimada, K., Miyata, H., Tobita, T., and Noda, T. (2019). CRISPR/Cas9-mediated genome editing reveals 30 testis-enriched genes dispensable for male fertility in mice. Biol. Reprod. 101, 501–511.
| CRISPR/Cas9-mediated genome editing reveals 30 testis-enriched genes dispensable for male fertility in mice.Crossref | GoogleScholarGoogle Scholar | 31201419PubMed |
Marks, M., Pennimpede, T., Lange, L., Grote, P., Herrmann, B. G., and Wittler, L. (2016). Analysis of the Fam181 gene family during mouse development reveals distinct strain-specific expression patterns, suggesting a role in nervous system development and function. Gene 575, 438–451.
| Analysis of the Fam181 gene family during mouse development reveals distinct strain-specific expression patterns, suggesting a role in nervous system development and function.Crossref | GoogleScholarGoogle Scholar | 26407640PubMed |
Nishimura, H., Kim, E., Nakanishi, T., and Baba, T. (2004). Possible function of the ADAM1a/ADAM2 fertilin complex in the appearance of ADAM3 on the sperm surface. J. Biol. Chem. 279, 34957–34962.
| Possible function of the ADAM1a/ADAM2 fertilin complex in the appearance of ADAM3 on the sperm surface.Crossref | GoogleScholarGoogle Scholar | 15194697PubMed |
Ozturk, S., Guzeloglu-Kayisli, O., Lowther, K. M., Lalioti, M. D., Sakkas, D., and Seli, E. (2014). Epab is dispensable for mouse spermatogenesis and male fertility. Mol. Reprod. Dev. 81, 390.
| Epab is dispensable for mouse spermatogenesis and male fertility.Crossref | GoogleScholarGoogle Scholar | 24599567PubMed |
Pasch, E., Link, J., Beck, C., Scheuerle, S., and Alsheimer, M. (2015). The LINC complex component Sun4 plays a crucial role in sperm head formation and fertility. Biol. Open 4, 1792–1802.
| The LINC complex component Sun4 plays a crucial role in sperm head formation and fertility.Crossref | GoogleScholarGoogle Scholar | 26621829PubMed |
Wagner, A. (2000). The role of population size, pleiotropy and fitness effects of mutations in the evolution of overlapping gene functions. Genetics 154, 1389–1401.
| The role of population size, pleiotropy and fitness effects of mutations in the evolution of overlapping gene functions.Crossref | GoogleScholarGoogle Scholar | 10757778PubMed |
Wang, H., Yang, H., Shivalila, C. S., Dawlaty, M. M., Cheng, A. W., Zhang, F., and Jaenisch, R. (2013). One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153, 910–918.
| One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering.Crossref | GoogleScholarGoogle Scholar | 23643243PubMed |
Wang, L., Iqbal, F., Li, G., Jiang, X., Bukhari, I., Jiang, H., Yang, Q., Zhong, L., Zhang, Y., Hua, J., Cooke, H. J., and Shi, Q. (2015). Abnormal meiotic recombination with complex chromosomal rearrangement in an azoospermic man. Reprod. Biomed. Online 30, 651–658.
| Abnormal meiotic recombination with complex chromosomal rearrangement in an azoospermic man.Crossref | GoogleScholarGoogle Scholar | 25892501PubMed |
Xia, B., Yan, Y., Baron, M., Wagner, F., Barkley, D., Chiodin, M., Kim, S. Y., Keefe, D. L., Alukal, J. P., and Boeke, J. (2020). Widespread transcriptional scanning in the testis modulates gene evolution rates. Cell 180, 248–262.e21.
| Widespread transcriptional scanning in the testis modulates gene evolution rates.Crossref | GoogleScholarGoogle Scholar | 31978344PubMed |
Xie, Y., Khan, R., Wahab, F., Hussain, H. M. J., Ali, A., Ma, H., Jiang, H., Xu, J., Zaman, Q., and Khan, M. (2019). The testis-specifically expressed Dpep3 is not essential for male fertility in mice. Gene 711, 143925.
| The testis-specifically expressed Dpep3 is not essential for male fertility in mice.Crossref | GoogleScholarGoogle Scholar | 31212048PubMed |
Yousaf, A., Wu, Y., Khan, R., Shah, W., Khan, I., Shi, Q., and Jiang, X. (2020). Normal spermatogenesis and fertility in Ddi1 (DNA damage inducible 1) mutant mice. Reprod. Biol. 20, 520–524.
| Normal spermatogenesis and fertility in Ddi1 (DNA damage inducible 1) mutant mice.Crossref | GoogleScholarGoogle Scholar | 33092996PubMed |
Zhu, Z., Zhang, X., Zeng, W., Zhao, S., Zhou, J., Zhou, Z., and Liu, M. (2020). Spermatogenesis is normal in Tex33 knockout mice. PeerJ 8, e9629.
| Spermatogenesis is normal in Tex33 knockout mice.Crossref | GoogleScholarGoogle Scholar | 32879807PubMed |
