Hfm1-KO Mouse

Hfm1, also known as helicase for meiosis 1 and POF9, is an ATP-dependent DNA helicase mainly expressed in germ-line cells. It is essential for crossover formation and completion of meiosis, participating in pathways related to ovarian development and meiosis/DNA repair. Genetic models, especially KO/CKO mouse models, have been crucial in studying its functions [1,2].

Specific knockout of Hfm1 in mouse oocytes from the primordial follicle stage led to depletion of ovarian follicular reserve and subfertility. Hfm1-cKO oocytes showed abnormal spindle, misaligned chromosomes, loss of cortical actin cap, and failing polar body extrusion. Hfm1 accumulates at the spindle poles, colocalized with the Golgi marker protein GM130, and its deficiency caused centrosome-associated proteins to detach from the spindle poles, indicating its role in Golgi-associated spindle assembly and division in mouse oocyte meiosis [1]. In addition, Hfm1 mutant female mice had infertility or subfertility with oogenesis affected, and Hfm1 variants in male mice led to meiotic arrest and non-obstructive azoospermia due to impaired crossover formation [2].

In conclusion, Hfm1 is essential for meiotic processes in both male and female germ cells. The KO/CKO mouse models have revealed its significance in ovarian follicular reserve, oocyte meiosis, and spermatogenesis, providing insights into the pathogenesis of premature ovarian failure, non-obstructive azoospermia, and related reproductive disorders [1,2].

References:

1. Wang, Huiyuan, Zhong, Chenyi, Yang, Rui, Pu, Danhua, Wu, Jie. 2020. Hfm1 participates in Golgi-associated spindle assembly and division in mouse oocyte meiosis. In Cell death & disease, 11, 490. doi:10.1038/s41419-020-2697-4. https://pubmed.ncbi.nlm.nih.gov/32606310/

2. Xie, Xuefeng, Murtaza, Ghulam, Li, Yang, Ma, Hui, Shi, Qinghua. . Biallelic HFM1 variants cause non-obstructive azoospermia with meiotic arrest in humans by impairing crossover formation to varying degrees. In Human reproduction (Oxford, England), 37, 1664-1677. doi:10.1093/humrep/deac092. https://pubmed.ncbi.nlm.nih.gov/35526155/