title: Scaffold attachment factor B1 functions in development, growth, and reproduction.
abstract: Scaffold attachment factor B1 (SAFB1) is a multifunctional protein that can bind both DNA and RNA and is involved in RNA processing and stress response. In addition, SAFB1 contains a transcriptional repression domain and can bind certain hormone receptors and repress their activity. To assess the role of SAFB1 in vivo, we generated SAFB1 mutant mice through targeted deletion in embryonic stem cells. While viable homozygous mutant (SAFB1-/-) mice were obtained, genotypic distribution indicated that homozygous deficiency resulted in both prenatal and neonatal lethality. Mice lacking SAFB1 exhibited dwarfism, as a result of in utero growth retardation, and had low serum insulin-like growth factor 1 (IGF1) levels. In agreement with the previous characterization of SAFB1 as a corepressor for hormone receptors, we found that SAFB1-/- mice displayed dramatic defects in the development and function of the reproductive system. Male SAFB1 null mice were infertile, apparently because of low circulating levels of testosterone. SAFB1-/- testes were small and showed progressive degeneration of the germinal epithelium, increased apoptosis of germ cells, and Leydig cell hyperplasia. SAFB-/- female mice were subfertile and showed progressive infertility, in part because of defects in oviductal transport and reduced numbers of follicles. Immortalized SAFB1-/- mouse embryonic fibroblasts showed cell-intrinsic defects including increased transcriptional estrogen receptor alpha activity and enhanced responsiveness to IGF1. Together, these in vivo findings establish a critical role for SAFB1 in development, growth regulation, and reproduction.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Breast Center, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Ivanova
authors.forename: Klaudia M
authors.initials: KM
authors.lastname: Dobrzycka
authors.forename: Shiming
authors.initials: S
authors.lastname: Jiang
authors.forename: Kai
authors.initials: K
authors.lastname: Michaelis
authors.forename: Rene
authors.initials: R
authors.lastname: Meyer
authors.forename: Kaiyan
authors.initials: K
authors.lastname: Kang
authors.forename: Brian
authors.initials: B
authors.lastname: Adkins
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Barski
authors.forename: Simeen
authors.initials: S
authors.lastname: Zubairy
authors.forename: Jana
authors.initials: J
authors.lastname: Divisova
authors.forename: Adrian V
authors.initials: AV
authors.lastname: Lee
authors.forename: Steffi
authors.initials: S
authors.lastname: Oesterreich
mesh_terms: D000818:Animals; D017209:Apoptosis; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004392:Dwarfism / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D005804:Genes, Lethal; D012739:Gonadal Steroid Hormones / Q000097:blood; D007247:Infertility, Female / Q000235:genetics; D007248:Infertility, Male / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism; D007985:Leydig Cells / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D012098:Reproduction / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D012739:Gonadal Steroid Hormones; D016601:RNA-Binding Proteins; C500609:scaffold attachment factor B1, mouse; D007334:Insulin-Like Growth Factor I