Tcfl5-KO Mouse

Tcfl5, a transcription factor, is crucial in male meiosis and spermatogenesis [1, 3-5]. It collaborates with factors like MYBL1 and A-MYB in gene regulatory networks, controlling meiotic entry, progression, and post-meiotic differentiation [1,3,4]. It also has roles in pathways related to piRNA production, mRNA turnover, and miR-34/449 production during spermatogenesis [3,4]. Mouse models have been valuable for studying its functions [2,4].

In mouse models, ubiquitous removal of Tcfl5 led to sterile males with meiosis arrest at the pachytene/diplotene transition, lack of spermatids, and altered testis architecture [2]. Tamoxifen-inducible Tcfl5 knockout mice also showed meiotic phenotypes and alterations in spermatid elongation [2]. Tcfl5-deficient mice had increased spermatogonia maintenance and meiosis genes, suggesting abnormal synaptonemal complex separation and meiotic progression [2]. Tcfl5em1/em1 mutants were sterile with meiotic arrest at mid-or late-pachytene, and Tcfl5+/em1 mutants had fewer motile sperm [4].

In conclusion, Tcfl5 is essential for spermatogenesis progression, meiosis resolution, and spermatid maturation in mice [2]. Understanding Tcfl5's role through these gene knockout mouse models may provide insights into male infertility, a disease area where its function is directly relevant.

References:

1. Säflund, Martin, Özata, Deniz M. . The MYBL1/TCFL5 transcription network: two collaborative factors with central role in male meiosis. In Biochemical Society transactions, 51, 2163-2172. doi:10.1042/BST20231007. https://pubmed.ncbi.nlm.nih.gov/38015556/

2. Galán-Martínez, Javier, Berenguer, Inés, Del Carmen Maza, Ma, Gironès, Núria, Fresno, Manuel. 2022. TCFL5 deficiency impairs the pachytene to diplotene transition during spermatogenesis in the mouse. In Scientific reports, 12, 10956. doi:10.1038/s41598-022-15167-w. https://pubmed.ncbi.nlm.nih.gov/35768632/

3. Yu, Tianxiong, Biasini, Adriano, Cecchini, Katharine, Zamore, Phillip D, Ozata, Deniz M. 2022. A-MYB/TCFL5 regulatory architecture ensures the production of pachytene piRNAs in placental mammals. In RNA (New York, N.Y.), 29, 30-43. doi:10.1261/rna.079472.122. https://pubmed.ncbi.nlm.nih.gov/36241367/

4. Cecchini, Katharine, Biasini, Adriano, Yu, Tianxiong, Zamore, Phillip D, Özata, Deniz M. 2023. The transcription factor TCFL5 responds to A-MYB to elaborate the male meiotic program in mice. In Reproduction (Cambridge, England), 165, 183-196. doi:10.1530/REP-22-0355. https://pubmed.ncbi.nlm.nih.gov/36395073/