title: The mouse meiotic mutation mei1 disrupts chromosome synapsis with sexually dimorphic consequences for meiotic progression.
abstract: mei1 (meiosis defective 1) is the first meiotic mutation in mice derived by phenotype-driven mutagenesis. It was isolated by using a novel technology in which embryonic stem (ES) cells were chemically mutagenized and used to generate families of mice that were screened for infertility. We report here that mei1/mei1 spermatocytes arrest at the zygotene stage of meiosis I, exhibiting failure of homologous chromosomes to properly synapse. Notably, RAD51 failed to associate with meiotic chromosomes in mutant spermatocytes, despite evidence for the presence of chromosomal breaks. Transcription of genes that are markers for the leptotene and zygotene stages, but not genes that are markers for the pachytene stage, was observed. mei1/mei1 females are sterile, and their oocytes also show severe synapsis defects. Nevertheless, unlike arrested spermatocytes, a small number of mutant oocytes proved capable of progressing to metaphase I and attempting the first meiotic division. However, their chromosomes were unpaired and were not organized properly at the metaphase plate or along the spindle fibers during segregation. mei1 was genetically mapped to chromosome (Chr) 15 in an interval that is syntenic to human Chr 22q13. This region, which has been completely sequenced, contains no known homologs of genes specifically required for meiosis in model organisms. Thus, mei1 may be a novel meiotic gene.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, 04609, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Libby
authors.forename: Rabindranath
authors.initials: R
authors.lastname: De La Fuente
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: O'Brien
authors.forename: Karen
authors.initials: K
authors.lastname: Wigglesworth
authors.forename: John
authors.initials: J
authors.lastname: Cobb
authors.forename: Amy
authors.initials: A
authors.lastname: Inselman
authors.forename: Shannon
authors.initials: S
authors.lastname: Eaker
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Handel
authors.forename: John J
authors.initials: JJ
authors.lastname: Eppig
authors.forename: John C
authors.initials: JC
authors.lastname: Schimenti
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D023902:Chromosome Pairing; D005455:Fluorescent Antibody Technique; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D008854:Microscopy, Electron; D009154:Mutation; D009865:Oocytes / Q000166:cytology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D013090:Spermatocytes / Q000648:ultrastructure; D014158:Transcription, Genetic