Germ cell‐specific disruption of the Meig1 gene causes impaired spermiogenesis in mice

Abstract

Summary Meiosis expressed gene 1 (Meig1) was originally identified in a search for mammalian genes potentially involved in meiosis. Seven mouse Meig1 transcripts with the same coding region, but different 5′-UTRs, have been identified. These transcripts have different tissue distributions, two are only present in the testis. In the testis, Meig1 is present in germ cells and Sertoli cells. A Meig1 conditional knockout model has been generated. When Meig1 was inactivated globally by crossing with Cmv-Cre transgenic mice, the Meig1-deficient males were sterile due to severe spermiogenic defects, and had no obvious defects in meiosis. To further study its role in individual cell types in the testis, the Meig1flox mice were crossed with Hsp2a-Cre, Prm-Cre, and Amh-Cre mice, in which the Cre recombinase is driven by the heat shock protein 2 (Hsp2a) gene promoter (expressed in spermatocytes), the protamine 1 gene promoter (expressed in post-meiotic spermatids) and the anti-Mullerian hormone (Amh) gene promoter (expressed in Sertoli cells) respectively. Both Meig1 mRNA and protein were undetectable in testis of the Hsp2a-Cre; Meig1flox/flox mice and all the mutant adult males tested were sterile. This phenotype mirrors that of the Cmv-Cre; Meig1flox/flox mice. Even though the total testicular Meig1 mRNA and protein expression levels were dramatically reduced in testis of the Prm-Cre; Meig1flox/flox males, all the mice tested were fertile, and there was no significant difference in sperm count and sperm motility compared with age-matched Meig1flox/flox male mice. Disruption of Meig1 in the Sertoli cells did not affect the MEIG1 protein expression. Amh-Cre; Meig1flox/flox males were fertile, and produced the same amount of spermatozoa as age-matched Meig1flox/flox mice. The testicular histology was also normal. Our results indicate that MEIG1 regulates spermiogenesis through effects in germ cells alone, and that the Meig1 gene must be active during a discrete period in spermatogenesis after which it is dispensable.

A MEIG1/PACRG complex in the manchette is essential for building the sperm flagella

“…Both laboratories discovered that MEIG1 regulates the final step of spermatogenesis, spermiogenesis. Even though Meig1 is also present in somatic cells in the testis ( Ever et al, 1999 ; Bouma et al, 2007 ), we discovered that MEIG1 regulates spermatogenesis through its role in germ cells, but not in Sertoli cells ( Teves et al, 2013 ). It has been reported that Meig1 is also expressed in embryonic mouse ovary ( Don et al, 1994 ; Chen-Moses et al, 1997 ), and MEIG1 mRNA expression is significantly altered in individuals with premature ovarian failure ( Ledig et al, 2010 ).…”

“…In the testis, Meig1 is expressed in somatic Sertoli cells and germ cells. Cell type-specific deletion of Meig1 gene in the testis demonstrated that the primary role of MEIG1 in the regulation of spermatogenesis is through germ cells ( Teves et al, 2013 ). Immunofluorescence studies on testicular sections and isolated mixed germ cells revealed that MEIG1 is present in the whole cell body in spermatocytes, but migrates to the manchette during the elongation/condensation process.…”

A Wisp3 Cre-knockin Allele Produces Efficient Recombination in Spermatocytes during Early Prophase of Meiosis I

“…The Wisp3 GFP-Cre allele produces minimal Cre-recombinase activity in cells/tissues other than spermatocytes, and thus Wisp3 GFP-Cre mice are unlikely to have significant off-target effects. This contrasts with transgenic strains containing Cre-drivers that are active during male meiosis I, such as Pgk2-Cre [25,26], Hspa2- Cre [27,28], and Synapsin-Cre [29]. These strains are efficient Cre-deleters during paternal transmission but they exhibit significant Cre-activity in multiple tissues during embryogenesis and post-natally, which can limit their usefulness in studying male spermatogenesis.…”

Dual functions of Intraflagellar Transport Protein IFT20 in spermiogenesis: formation of sperm flagella and removal of cytoplasm by autophagy

“…Our laboratory identified a MEIG1/PACRG complex in male germ cells during the study of cargo transport along the manchette and sperm flagellum formation (Zhang et al, 2009;Teves et al, 2013;Li et al, 2015;Li et al, 2016). It appears that the roles of the MEIG1/PACRG complex and IFT proteins overlap in the transport of cargo during the assembly of cilia and flagella.…”