Positional cloning and characterization of mouse mei8, a disrupted allelle of the meiotic cohesin Rec8

Area of Science:

• Genetics
• Reproductive Biology
• Cell Biology

Background:

• Infertility can arise from genetic mutations affecting meiosis.
• The cohesin complex, including REC8, plays a vital role in chromosome segregation during cell division.

Purpose of the Study:

• To identify the genetic cause of infertility in mice with the novel mei8 mutation.
• To investigate the function of the REC8 gene in mammalian meiosis.

Main Methods:

• Forward genetic screen using chemical mutagenesis of ES cells.
• Genetic mapping and positional cloning to identify the mutated gene.
• Meiotic analysis of Rec8(mei8)/Rec8(mei8) mutant mice.

Main Results:

• The mei8 mutation was identified in the Rec8 gene, a homolog of yeast REC8.
• Homozygous mutant mice are sterile, with females showing ovarian dysgenesis and males exhibiting spermatogenesis arrest.
• REC8 is essential for synapsis completion, sister chromatid cohesion, and chiasma formation in mouse meiosis.
• Unlike in yeast and C. elegans, REC8 localization is not required for axial element assembly in mice.

Conclusions:

• The study identifies a novel mutation in the mouse Rec8 gene responsible for infertility.
• Mammalian REC8 is critical for key meiotic processes, including synapsis and chromosome cohesion.
• Mouse meiosis exhibits some distinct features compared to other model organisms regarding REC8 function.