<i>Mili</i>, a mammalian member of<i>piwi</i>family gene, is essential for spermatogenesis

TLDR

The piwi family genes, defined by conserved PAZ and Piwi domains, are key regulators of stem cell self‑renewal, RNA silencing, and translational control across species. The study aimed to uncover the function of the mammalian Piwi homolog Mili. This was achieved by generating and analyzing mice with targeted mutations in the Mili gene. MILI is essential for spermatocyte differentiation, as its loss blocks spermatogenesis at early prophase of meiosis I, causing sterility, while primordial germ cell development and female germ cells remain unaffected, and MILI physically associates with MVH, mirroring MVH‑deficient phenotypes.

Abstract

The piwi family genes, which are defined by conserved PAZ and Piwi domains, play important roles in stem cell self-renewal, RNA silencing, and translational regulation in various organisms. To reveal the function of the mammalian homolog of piwi, we produced and analyzed mice with targeted mutations in the Mili gene, which is one of three mouse homologs of piwi. Spermatogenesis in the MILI-null mice was blocked completely at the early prophase of the first meiosis, from the zygotene to early pachytene, and the mice were sterile. However, primordial germ cell development and female germ cell production were not disturbed. Furthermore, MILI bound to MVH, which is an essential factor during the early spermatocyte stage. The similarities in the phenotypes of the MILI- and MVH-deficient mice and in the physical binding properties of MILI and MVH indicate a functional association of these proteins in post-transcriptional regulation. These data indicate that MILI is essential for the differentiation of spermatocytes.