Psma8-flox Mouse

Psma8, also known as α4s, is a testis-specific proteasomal subunit. It is crucial for proper meiotic exit during spermatogenesis, with its associated proteasomes being essential for the degradation of meiotic proteins and the progression of meiosis I. This process is tightly regulated by ubiquitination and proteasomal degradation, and Psma8-containing proteasomes are involved in histone degradation during DNA repair in spermatocytes [1,2,3].

In Psma8-deficient mice, meiotic homologous recombination is proficient, but there are alterations in the proteostasis of key meiotic players like SYCP3, SYCP1, CDK1, and TRIP13. This leads to an accumulation of spermatocytes in metaphase I and II, resulting in either massive apoptosis or the generation of a low number of aberrant round spermatids that apoptose before histone replacement. Additionally, deletion of Psma8 decreases the abundance of proteasome in testes, and meiotic proteins that should be degraded at late prophase I remain stable, causing male infertility as spermatocytes are arrested at the M-phase. However, Psma8 is neither expressed nor required for female meiotic progression [1,2].

In conclusion, Psma8 is essential for the proper progression of meiosis during spermatogenesis, specifically for the degradation of meiotic proteins and histone degradation at DNA damage loci. The study of Psma8-deficient mouse models has provided valuable insights into male infertility, highlighting its potential as a target for male contraception or treatment of male infertility.