The dual bromodomain and WD repeat-containing mouse protein BRWD1 is required for normal spermiogenesis and the oocyte–embryo transition
| Autor: | Suzanne Hartford, Kerry J. Schimenti, Dana L. Philipps, John J. Eppig, Shrivatsav Pattabiraman, Fengyun Sun, John C. Schimenti, Mary Ann Handel, Karen Wigglesworth |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Mouse Positional cloning Spermiogenesis Mutant Bromodomain medicine.disease_cause Article Chromatin remodeling Mice 03 medical and health sciences Oogenesis 0302 clinical medicine medicine Animals Cloning Molecular Spermatogenesis Molecular Biology 030304 developmental biology Sex Characteristics 0303 health sciences Mutation 030219 obstetrics & reproductive medicine biology Cell Biology Molecular biology Chromatin Mice Inbred C57BL Meiosis Histone Mutagenesis Infertility Ethylnitrosourea Oocytes biology.protein Developmental Biology Genetic screen |
| Zdroj: | Developmental Biology. 317:72-82 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2008.02.018 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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