Dis3-flox Mouse

DIS3, an exoribonuclease, is the catalytic subunit of the exosome complex crucial for the 3' to 5' degradation and processing of nuclear and cytoplasmic RNA species. It is involved in RNA homeostasis, and its proper function is vital for normal cell-cycle progression, hematopoiesis, and development [1,7]. Genetic models, especially knockout mouse models, have been instrumental in studying its functions.

In multiple myeloma (MM), DIS3 mutations are found in about 10% of patients, and del(13q) affecting DIS3 expression occurs in around 40% of cases. DIS3 knockdown in MM cell lines inhibits proliferation, disrupts cell cycle progression, and causes centrosome amplification, potentially leading to genomic instability [1,3,4]. In male mice, germ-cell Dis3 conditional knockout (cKO) disrupts spermatogenesis, leading to a Sertoli cell-only phenotype and sterility, indicating its essential role in male germ cell lineage maintenance [2]. In contrast, DIS3 deficiency in the initial segment of the epididymis has no effect on sperm maturation or male fertility [5]. In pre-implantation mouse embryos, Dis3 knockout leads to embryo arrest at the morula stage due to the persistence of Pou6f1 mRNA, highlighting its role in cell differentiation [6]. DIS3 knockdown in Drosophila ovaries results in lack of oocyte production and severe infertility, suggesting its role in oogenesis [8].

In conclusion, DIS3 is essential for RNA metabolism, cell-cycle regulation, and normal development in various biological processes. Mouse KO/CKO models have significantly contributed to understanding its role in multiple myeloma, spermatogenesis, pre-implantation development, and oogenesis. These findings enhance our knowledge of DIS3's biological functions and its implications in disease conditions.