title: The dual bromodomain and WD repeat-containing mouse protein BRWD1 is required for normal spermiogenesis and the oocyte-embryo transition.
abstract: A novel mutation, repro5, was isolated in a forward genetic screen for infertility mutations induced by ENU mutagenesis. Homozygous mutant mice were phenotypically normal but were infertile. Oocytes from mutant females appeared normal, but were severely maturation-defective in that they had reduced ability to progress to metaphase II (MII), and those reaching MII were unable to progress beyond the two pronuclei stage following in vitro fertilization (IVF). Mutant males exhibited defective spermiogenesis, resulting in oligoasthenoteratospermia. Genetic mapping, positional cloning, and complementation studies with a disruption allele led to the identification of a mutation in Brwd1 (Bromodomain and WD repeat domain containing 1) as the causative lesion. Bromodomain-containing proteins typically interact with regions of chromatin containing histones hyperacetylated at lysine residues, a characteristic of chromatin in early spermiogenesis before eventual replacement of histones by the protamines. Previous data indicated that Brwd1 is broadly expressed, encoding a putative transcriptional regulator that is believed to act on chromatin through interactions with the Brg1-dependent SWI/SNF chromatin-remodeling pathway. Brwd1 represents one of a small number of genes whose elimination disrupts gametogenesis in both sexes after the major events of meiotic prophase I have been completed.
authors: Cornell University, College of Veterinary Medicine, Ithaca, NY 14850, USA.
authors: Dana L
authors: DL
authors: Philipps
authors: Karen
authors: K
authors: Wigglesworth
authors: Suzanne A
authors: SA
authors: Hartford
authors: Fengyun
authors: F
authors: Sun
authors: Shrivatsav
authors: S
authors: Pattabiraman
authors: Kerry
authors: K
authors: Schimenti
authors: MaryAnn
authors: M
authors: Handel
authors: John J
authors: JJ
authors: Eppig
authors: John C
authors: JC
authors: Schimenti
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D005038:Ethylnitrosourea; D008297:Male; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D009866:Oogenesis; D012727:Sex Characteristics; D013091:Spermatogenesis
chemical_list: D005038:Ethylnitrosourea