Nup210l-KO Mouse

NUP210L, encoding a testis-specific nucleoporin, is likely involved in nuclear trafficking. It may be crucial for regulating nuclear trafficking during and/or before spermiogenesis, potentially impacting nuclear compaction in spermatozoa [2,4].

In a study of an infertile man, a homozygous loss-of-function variant in NUP210L led to highly uncondensed sperm nuclear DNA, while in Nup210l null allele mice, spermatozoa showed mild anomalies in head morphology and decreased motility, but normal nuclear compaction and histone removal [2,4]. This suggests that NUP210L alone may not block spermatid nuclear compaction. Additionally, in a TWAS in African-ancestry female participants, NUP210L was identified as a putative breast cancer susceptibility gene, with a stronger association with estrogen-receptor negative or triple-negative breast cancer [1]. It was also found among genes with differential methylation in young adults with tinnitus, and was highlighted as a potential mediator of the genetic correlation between major depressive disorders and anxiety and stress-related disorders [3,5].

In summary, NUP210L appears to be important for male fertility, potentially through its role in sperm nuclear compaction. Its association with breast cancer, tinnitus, and mental disorders indicates its significance in multiple disease areas. Mouse models have been valuable in understanding its function in male fertility, shedding light on the complex mechanisms underlying sperm development and the role of NUP210L in certain disease susceptibilities.