Meig1 deficiency causes a severe defect in mouse spermatogenesis

Meig1 is a mouse gene, abundantly expressed in the testis. It encodes two alternative transcripts that are expressed differentially in the somatic and germinal compartments of the testis. These transcripts share the same coding region but differ in their 5′ un-translated regions, due to alternative promoters. Here we show that MEIG1 is a highly conserved short metazoan protein with a conserved core of 81 residues. It is present from chordates to radial symmetry animals, with an intriguing absence in insects and nematodes. It is also present in two earlier diverging protist lineages. To elucidate the role of MEIG1 during gamete production we established a knockout mouse line by eliminating the common coding region. Our results identified Meig1 as a critical spermatogenic gene, whose absence results in complete male infertility. Seminiferous tubules in Meig1-null males contained all early stages of spermatogenesis, up to elongating spermatids, but mature elongated spermatids were absent. Accordingly, the caudal epididymis was apparently missing spermatozoa, and the very few spermatozoa-like cells that were obtained were immotile and exhibited a wide range of severe morphological abnormalities. These results point at late spermiogenesis as the differentiative stage at which MEIG1's function is crucial. Nevertheless, delayed kinetics of earlier meiotic stages together with increased apoptosis of meiotic spermatocytes and haploid round spermadids in Meig1 knockout males, suggest involvement of MEIG1 in meiotic stages as well.