Abstract:
:Mice carrying a germ-line null mutation of the prolactin receptor gene have been produced by gene targeting in embryonic stem cells. Heterozygous females showed almost complete failure of lactation attributable to greatly reduced mammary gland development after their first, but not subsequent, pregnancies. Homozygous females were sterile owing to a complete failure of embryonic implantation. Moreover, they presented multiple reproductive abnormalities, including irregular cycles, reduced fertilization rates, defective preimplantation embryonic development, and lack of pseudopregnancy. Half of the homozygous males were infertile or showed reduced fertility. This work establishes the prolactin receptor as a key regulator of mammalian reproduction, and provides the first total ablation model to further study the role of the prolactin receptor and its ligands.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Ormandy CJ,Camus A,Barra J,Damotte D,Lucas B,Buteau H,Edery M,Brousse N,Babinet C,Binart N,Kelly PAdoi
10.1101/gad.11.2.167subject
Has Abstractpub_date
1997-01-15 00:00:00pages
167-78issue
2eissn
0890-9369issn
1549-5477journal_volume
11pub_type
杂志文章abstract::Smads regulate transcription of defined genes in response to TGF-beta receptor activation, although the mechanisms of Smad-mediated transcription are not well understood. We demonstrate that the TGF-beta-inducible Smad3 uses the tumor suppressor Smad4/DPC4 and CBP/p300 as transcriptional coactivators, which associate ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.14.2153
更新日期:1998-07-15 00:00:00
abstract::Faithful duplication of the genome relies on the ability to cope with an imperfect template. We investigated replication of UV-damaged DNA in Escherichia coli and found that ongoing replication stops for at least 15-20 min before resuming. Undamaged origins of replication (oriC) continue to fire at the normal rate and...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.417607
更新日期:2007-03-15 00:00:00
abstract::Genomic imprinting is an epigenetic process regulated by germline-derived DNA methylation, causing parental origin-specific monoallelic gene expression. Zinc finger protein 57 (ZFP57) is critical for maintenance of this epigenetic memory during post-fertilization reprogramming, yet incomplete penetrance of ZFP57 mutat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.320069.118
更新日期:2019-01-01 00:00:00
abstract::Cell fates in the optic neuroepithelium are determined by the combinational action of homeotic transcription factors. One of these is Vax2, a homeodomain protein that ventralizes the vertebrate eye field by repressing transcription of the Pax6 gene. We find that Vax2 shuttles between the nucleus and cytoplasm as a fun...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1462706
更新日期:2006-10-15 00:00:00
abstract::The Elongin BC complex was identified initially as a positive regulator of RNA polymerase II (Pol II) elongation factor Elongin A and subsequently as a component of the multiprotein von Hippel-Lindau (VHL) tumor suppressor complex, in which it participates in both tumor suppression and negative regulation of hypoxia-i...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.24.3872
更新日期:1998-12-15 00:00:00
abstract::Post-translational modifications of conserved N-terminal tail residues in histones regulate many aspects of chromosome activity. Thr 3 of histone H3 is highly conserved, but the significance of its phosphorylation is unclear, and the identity of the corresponding kinase unknown. Immunostaining with phospho-specific an...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1267105
更新日期:2005-02-15 00:00:00
abstract::The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.257675.114
更新日期:2015-04-15 00:00:00
abstract::Jun and Fos oncoproteins form a complex that regulates transcription from promoters containing AP-1 binding sites. The 'leucine zipper' domain of both Fos and Jun is necessary for the formation of the heterodimer, but the role of specific leucine residues is unclear. We have used site-specific mutagenesis to examine t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.6.770
更新日期:1989-06-01 00:00:00
abstract::Specific recognition of splice sites within metazoan mRNA precursors (pre-mRNAs) is a potential stage for gene regulation by alternative splicing. Splicing factors of the SR protein family play a major role in this regulation, as they are required for early recognition of splice sites during spliceosome assembly. Here...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.6.740
更新日期:1999-03-15 00:00:00
abstract::TGF-β receptors phosphorylate SMAD2 and SMAD3 transcription factors, which then form heterotrimeric complexes with SMAD4 and cooperate with context-specific transcription factors to activate target genes. Here we provide biochemical and structural evidence showing that binding of SMAD2 to DNA depends on the conformati...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.330837.119
更新日期:2019-11-01 00:00:00
abstract::Signals from TGF-beta superfamily receptors are transduced to the nucleus by Smad proteins, which transcriptionally activate target genes. In Caenorhabditis elegans, defects in a TGF-beta-related pathway cause a reversible developmental arrest and metabolic shift at the dauer larval stage. Null mutations in daf-3 supp...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.20.2679
更新日期:1997-10-15 00:00:00
abstract::We have purified and cloned a new splicing factor, KSRP. KSRP is a component of a multiprotein complex that binds specifically to an intronic splicing enhancer element downstream of the neuron-specific c-src N1 exon. This 75-kD protein induces the assembly of five other proteins, including the heterogeneous nuclear ri...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.8.1023
更新日期:1997-04-15 00:00:00
abstract::Exposure of hematopoietic progenitors to gamma-irradiation (IR) induces p53-dependent apoptosis and a p53-independent G2/M cell cycle arrest. These responses to DNA-damage can be inhibited by treatment with cytokine growth factors. Here we report that gamma-IR-induced apoptosis and cell cycle arrest are suppressed by ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.8.1099
更新日期:1998-04-15 00:00:00
abstract::A cDNA library enriched for transcripts that accumulate from embryonic day 7 until day 1 posthatching was constructed from poly(A)+ RNA of chick optic lobe tissue. From this library, three recombinants were isolated that correspond to neural mRNAs appearing during the major period of synaptogenesis in the retinotectal...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.7.699
更新日期:1987-09-01 00:00:00
abstract::Mutations in the CSA or CSB complementation genes cause the Cockayne syndrome, a severe genetic disorder that results in patients' death in early adulthood. CSA and CSB act in a transcription-coupled repair (TCR) pathway, but their functional relationship is not understood. We have previously shown that CSA is a subun...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.378206
更新日期:2006-06-01 00:00:00
abstract::The agouti gene regulates the differential production of eumelanin (black or brown) and phaeomelanin (yellow) pigment granules by melanocytes in the hair follicles of mice. The original nonagouti (a) allele, which confers a predominantly black coat color, has been shown to revert to two other more dominant agouti alle...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.4.481
更新日期:1994-02-15 00:00:00
abstract::Plant water homeostasis is maintained by the phytohormone abscisic acid (ABA), which triggers stomatal pore closure in response to drought stress. We identified the Arabidopsis small guanosine triphosphatase (GTPase) protein AtRac1 as a central component in the ABA-mediated stomatal closure process. ABA treatment indu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.900401
更新日期:2001-07-15 00:00:00
abstract::Gene silencing by double-stranded RNA is a widespread phenomenon called RNAi, involving homology-dependent degradation of mRNAs. Here we show that RNAi is established in the Drosophila female germ line. mRNA transcripts are translationally quiescent at the arrested oocyte stage and are insensitive to RNAi. Upon oocyte...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.990802
更新日期:2002-08-01 00:00:00
abstract::In somatic cells of Xenopus, transcription of the TFIIIA gene initiates greater than 200 bp upstream from the start site used in oocytes. The resultant mRNA encodes a protein, S-TFIIIA, that is 22 amino acids longer at its amino terminus than the abundant form of TFIIIA in oocytes (O-TFIIIA). S-TFIIIA binds the 5S RNA...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.9.1602
更新日期:1990-09-01 00:00:00
abstract::Atypical teratoid rhabdoid tumors (ATRTs) are challenging pediatric brain cancers that are predominantly associated with inactivation of the gene SMARCB1, a conserved subunit of the chromatin remodeling BAF complex, which has known contributions to developmental processes. To identify potential interactions between SM...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.339978.120
更新日期:2020-10-01 00:00:00
abstract::The association of proteins with the branch site region during pre-mRNA splicing was probed using a novel methodology to site-specifically modify the pre-mRNA with the photo-reagent benzophenone. Three sets of proteins were distinguished by the kinetics of their associations with pre-mRNAs, by their association with d...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.24.3008
更新日期:1994-12-15 00:00:00
abstract::The product of the zygotically active decapentaplegic (dpp) gene appears to function as a morphogen that specifies positional information in the dorsal half of the Drosophila embryo. The dorsal-specific transcription of dpp is the key step in establishing a morphogen gradient. We demonstrate here that multiple regions...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.4.694
更新日期:1993-04-01 00:00:00
abstract::eIF2B is a heteropentameric guanine-nucleotide exchange factor essential for protein synthesis initiation in eukaryotes. Its activity is inhibited in response to starvation or stress by phosphorylation of the alpha subunit of its substrate, translation initiation factor eIF2, resulting in reduced rates of translation ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.4.514
更新日期:1998-02-15 00:00:00
abstract::Natural scrapie has been viewed both as a recessive trait and as a contagious disease modulated by a host locus. To address this conundrum, we determined the structure of the sheep prion protein (PrP) gene, which contains three exons and extends over 20 kb of DNA. In the United States 86.4% of scrapie cases occur in S...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.8.959
更新日期:1994-04-15 00:00:00
abstract::Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a unique opportunity to derive patient-specific stem cells with potential applications in tissue replacement therapies and without the ethical concerns of human embryonic stem cells (hESCs). However, cellular senescence, which c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.173922.111
更新日期:2011-11-01 00:00:00
abstract::The SNF1 protein kinase is broadly conserved in eukaryotes and has been implicated in responses to environmental and nutritional stress. In yeast, the SNF1 kinase has a central role in the response to glucose starvation. SNF1 is associated with its activating subunit, SNF4, and other proteins in complexes. Using the t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.24.3105
更新日期:1996-12-15 00:00:00
abstract::The RAG-1 protein plays an essential role in V(D)j recombination, but its exact function has not yet been defined. Here we report that a particular mutation in RAG-1 affects recombination by altering the specificity of target sequence usage. Recombination mediated by wild-type RAG-1 is tolerant of a wide range of codi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.17.2193
更新日期:1995-09-01 00:00:00
abstract::Cells have evolved checkpoint responses to arrest or delay the cell cycle, activate DNA repair networks, or induce apoptosis after genomic perturbation. Cells have also evolved the translesion synthesis processes to tolerate genomic lesions by either error-free or error-prone repair. Here, we show that after a replica...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1043203
更新日期:2003-01-01 00:00:00
abstract::DOCK180 is involved in integrin signaling through CrkII-p130(Cas) complexes. We have studied the involvement of DOCK180 in Rac1 signaling cascades. DOCK180 activated JNK in a manner dependent on Rac1, Cdc42Hs, and SEK, and overexpression of DOCK180 increased the amount of GTP-bound Rac1 in 293T cells. Coexpression of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.21.3331
更新日期:1998-11-01 00:00:00
abstract::In Saccharomyces cerevisiae, short noncoding RNA (ncRNA) generated by RNA polymerase II (Pol II) are terminated by the NRD complex consisting of Nrd1, Nab3, and Sen1. We now show that Pcf11, a component of the cleavage and polyadenylation complex (CPAC), is also generally required for NRD-dependent transcription termi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.251470.114
更新日期:2015-04-15 00:00:00