Hnrnph1, encoding heterogeneous nuclear ribonucleoprotein H1, is an RNA-binding protein involved in all stages of RNA metabolism. It plays a role in multiple biological pathways, such as alternative pre-mRNA splicing, mitochondrial-nuclear communication, and stress response regulation. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions [2].

In germ cells, conditional knockout of Hnrnph1 in spermatogenic cells causes abnormal splicing events, affecting meiosis-related genes and germ-Sertoli cell communication, leading to male sterility. Hnrnph1-deficient oocytes also show defective synapsis and cell-cell junctions, causing female infertility [1].

In Sertoli cells, conditional knockout of Hnrnph1 leads to compromised blood-testis barrier function, delayed meiotic progression, increased germ cell apoptosis, and infertility in mice. Hnrnph1 interacts with PTBP1 to regulate pre-mRNA alternative splicing of cell-adhesion-related genes and cooperates with the androgen receptor to modulate the transcription of genes associated with cell-cell junctions and the EGFR pathway [3].

In addition, deletion of Hnrnph1 in mice affects alcohol-related behaviors, such as blunted intake of high-alcohol concentrations in male mice and reversal of high-dose alcohol-induced conditioned place-aversion [2].

In conclusion, Hnrnph1 is essential for germ cell development and male fertility as revealed by KO/CKO mouse models. It also has an impact on alcohol-related behaviors. These model-based studies contribute to understanding the roles of Hnrnph1 in reproductive and addiction-related disease areas.