Rlim, also known as Rnf12, is an X-linked E3 ubiquitin ligase. It is crucial for X chromosome inactivation (XCI), a process that silences one of the two X chromosomes in female mammals for dosage compensation. Rlim is involved in the transcriptional activation of Xist, a long non-coding RNA essential for XCI [1,2,4,5].

Systemic knockout (KO) of Rlim in female mice leads to death around implantation, while male KO mice seem healthy but have deficient spermiogenesis with lower numbers of mature sperm, decreased sperm motility, and in vitro fertilization rates [3]. In female mouse embryogenesis, Rlim is important for imprinted XCI (iXCI) in extraembryonic tissues. Conditional knockout (CKO) specifically in the spermatogenic cell lineage recapitulates the spermiogenesis-related phenotype, revealing its function in male reproduction during spermiogenesis [3]. Additionally, inactivation of the maternal Rlim allele in embryos results in a male-biased sex ratio skew in the offspring, but also reduces litter size [6].

In conclusion, Rlim plays essential roles in XCI during female mouse development and in spermiogenesis in male mice. The study of Rlim using KO and CKO mouse models has provided insights into its functions in these biological processes, which are relevant to understanding sex-related development and male reproductive diseases [3,6].