Loss Of Chromodomain of Male-Specific Lethal 3 (MSL3) Does Not Affect Spermatogenesis In Rodents

Area of Science:

• Reproductive biology
• Chromatin biology
• Gene regulation

Background:

• The male-specific lethal 3 (Msl3) protein is a conserved component of the dosage compensation complex, essential for X-chromosome transcriptional upregulation in Drosophila males.
• While Msl3's role in meiotic entry is established in Drosophila oogenesis and suggested in primate germline cells, its function in mammalian male meiosis remains unexplored.
• Msl3 is conserved across species, indicating potential shared biological functions despite differing roles in dosage compensation between flies and mammals.

Approach:

• Investigated Msl3's role in mammalian male meiosis using mouse spermatogenesis as a model system.
• Analyzed single-cell RNA-seq data to determine Msl3 expression patterns during mouse spermatogenesis, identifying expression primarily in meiotic cells.
• Generated a novel Msl3 conditional knockout mouse line utilizing a Stra8-iCre driver to specifically delete Msl3 in the male germline.

Key Points:

• Msl3 expression in mice is predominantly observed in meiotic cells, suggesting a potential role in this process.
• Conditional knockout of Msl3 in spermatogonia did not lead to observable defects in spermatogenesis.
• Disruption of Msl3, including its chromodomain, did not impede meiotic entry in male mice.

Conclusions:

• Msl3 exhibits delayed expression in mouse spermatogenesis compared to Drosophila and primates.
• Msl3 is not essential for initiating meiosis in the male mouse germline.
• The function of Msl3 in mammalian male meiosis differs from its established role in Drosophila oogenesis and suggested roles in primates.