GENETICS OF MEIOSIS AND RECOMBINATION IN MICE

Meiosis is one of the most critical developmental processes in sexually reproducing organisms. One round of DNA replication followed by two rounds of cell divisions results in generation of haploid gametes (sperm and eggs in mammals). Meiotic failure typically leads to infertility in mammals. In the process of meiotic recombination, maternal and paternal genomes are shuffled, creating new allelic combinations and thus genetic variety. However, in order to achieve this, meiotic cells must self-inflict DNA damage in the form of programmed double-strand breaks (DSBs). Complex processes evolved to ensure proper DSB repair, and to do so in a way that favors interhomolog reciprocal recombination and crossovers. The hallmark of meiosis, a structurally conserved proteinaceous structure called the synaptonemal complex, is found only in meiotic cells. Conversely, meiotic homologous recombination is an adaptation of the mitotic DNA repair process but involving specialized proteins. In this chapter, we summarize current developments in mammalian meiosis enabled by genetically modified mice.