A germ-line insertion in the Birt-Hogg-Dubé (BHD) gene gives rise to the Nihon rat model of inherited renal cancer.

Abstract:

:A rat model of hereditary renal carcinoma (RC) was found in a rat colony of the Sprague-Dawley strain in Japan and named the "Nihon" rat. In heterozygotes, RCs, predominantly the clear cell type, develop from early preneoplastic lesions, which began to appear as early as 3 weeks of age, to adenocarcinomas by the age of 6 months. The Nihon rat is an example of a Mendelian dominantly inherited predisposition for development of RCs like the Eker (Tsc2 gene mutant) rat. We have previously shown that the Nihon mutation was tightly linked to genes that are located on the distal part of rat chromosome 10. The order of the genes is the Eker (Tsc2 gene (human 16p13.3)-Il3 gene-Nihon gene-Llgl1 locus- Myhse gene. We now describe a germ-line mutation in the Birt-Hogg-Dubé gene (Bhd) (human 17p11.2) caused by the insertion of a single nucleotide in the Nihon rat, resulting in a frameshift and producing a stop codon 26 aa downstream. We found that the homozygous mutant condition was lethal at an early stage of fetal life in the rat. We detected a high frequency of loss of heterozygosity (LOH) in primary RCs (10/11) at the Bhd locus and found a point mutation (nonsense) in one LOH-negative case, fitting Knudson's "two-hit" model. The Nihon rat may therefore provide insights into a tumor-suppressor gene that is related to renal carcinogenesis and an animal model of human BHD syndrome.

authors

Okimoto K,Sakurai J,Kobayashi T,Mitani H,Hirayama Y,Nickerson ML,Warren MB,Zbar B,Schmidt LS,Hino O

doi

10.1073/pnas.0308071100

keywords:

subject

Has Abstract

pub_date

2004-02-17 00:00:00

pages

2023-7

issue

7

eissn

0027-8424

issn

1091-6490

pii

0308071100

journal_volume

101

pub_type

杂志文章
  • A helical-dipole model describes the single-channel current rectification of an uncharged peptide ion channel.

    abstract::We are designing simple peptide ion channels as model systems for the study of the physical principles controlling conduction through ion-channel proteins. Here we report on an uncharged peptide, Ac-(Leu-Ser-Ser-Leu-Leu-Ser-Leu)3-CONH2, designed to form an aggregate of parallel, amphiphilic, membrane-spanning alpha-he...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.11.4859

    authors: Kienker PK,DeGrado WF,Lear JD

    更新日期:1994-05-24 00:00:00

  • The spectrum of seminormal operators.

    abstract::With every pair of bounded self-adjoint operators {U,V} on Hilbert space such that VU - UV = (1/pii)C, where C is trace class, there is associated a certain function of two complex variables called the determining function of the pair. It was previously shown how the determining function can be obtained as the solutio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.68.8.1684

    authors: Pincus JD

    更新日期:1971-08-01 00:00:00

  • Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity.

    abstract::Neuropilin-1 (NRP1) is a 130-kDa transmembrane receptor for semaphorins, mediators of neuronal guidance, and for vascular endothelial growth factor 165 (VEGF(165)), an angiogenesis factor. A 2.2-kb truncated NRP1 cDNA was cloned that encodes a 644-aa soluble NRP1 (sNRP1) isoform containing just the a/CUB and b/coagula...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.040337597

    authors: Gagnon ML,Bielenberg DR,Gechtman Z,Miao HQ,Takashima S,Soker S,Klagsbrun M

    更新日期:2000-03-14 00:00:00

  • Dynamics of transient pores in stretched vesicles.

    abstract::We image macroscopic transient pores in mechanically stretched giant vesicles. Holes open above a critical radius r(c1), grow up to a radius r(c2), and close. We interpret the upper limit r(c2) by a relaxation of the membrane tension as the holes expand. The closing of the holes is caused by a further relaxation of th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.19.10591

    authors: Sandre O,Moreaux L,Brochard-Wyart F

    更新日期:1999-09-14 00:00:00

  • N-cadherin-dependent neuron-neuron interaction is required for the maintenance of activity-induced dendrite growth.

    abstract::Formation of neural circuits depends on stable contacts between neuronal processes, mediated by interaction of cell adhesion molecules, including N-cadherin. In the present study, we found that activity-dependent dendrite arborization specifically requires N-cadherin-mediated extracellular neuron-neuron interaction, b...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1003480107

    authors: Tan ZJ,Peng Y,Song HL,Zheng JJ,Yu X

    更新日期:2010-05-25 00:00:00

  • Ultrahigh-throughput screening in drop-based microfluidics for directed evolution.

    abstract::The explosive growth in our knowledge of genomes, proteomes, and metabolomes is driving ever-increasing fundamental understanding of the biochemistry of life, enabling qualitatively new studies of complex biological systems and their evolution. This knowledge also drives modern biotechnologies, such as molecular engin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0910781107

    authors: Agresti JJ,Antipov E,Abate AR,Ahn K,Rowat AC,Baret JC,Marquez M,Klibanov AM,Griffiths AD,Weitz DA

    更新日期:2010-03-02 00:00:00

  • Light induces rapid changes of the phosphorylation pattern in the cytosol of evacuolated parsley protoplasts.

    abstract::The fractionation of cells of a parsley suspension culture [Petroselinum crispum (Mill.) A. Hill] by protoplasting and subsequent removal of the vacuoles led to physiologically intact evacuolated protoplasts retaining light inducibility of chalcone synthase expression. Lysis of the evacuolated protoplasts permitted th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.11.5038

    authors: Harter K,Frohnmeyer H,Kircher S,Kunkel T,Mühlbauer S,Schäfer E

    更新日期:1994-05-24 00:00:00

  • Spiral structure of Escherichia coli HUalphabeta provides foundation for DNA supercoiling.

    abstract::We determined the crystal structure of the Escherichia coli nucleoid-associated HUalphabeta protein by x-ray diffraction and observed that the heterodimers form multimers with octameric units in three potential arrangements, which may serve specialized roles in different DNA transaction reactions. It is of special imp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0611686104

    authors: Guo F,Adhya S

    更新日期:2007-03-13 00:00:00

  • REM sleep's unique associations with corticosterone regulation, apoptotic pathways, and behavior in chronic stress in mice.

    abstract::One of sleep's putative functions is mediation of adaptation to waking experiences. Chronic stress is a common waking experience; however, which specific aspect of sleep is most responsive, and how sleep changes relate to behavioral disturbances and molecular correlates remain unknown. We quantified sleep, physical, e...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1816456116

    authors: Nollet M,Hicks H,McCarthy AP,Wu H,Möller-Levet CS,Laing EE,Malki K,Lawless N,Wafford KA,Dijk DJ,Winsky-Sommerer R

    更新日期:2019-02-12 00:00:00

  • The sizes of the CDR3 hypervariable regions of the murine T-cell receptor beta chains vary as a function of the recombined germ-line segments.

    abstract::A method using PCR amplification and primer extension with fluorescent oligonucleotides was developed to analyze T-cell repertoires. The sizes of the hypervariable CDR3-like regions of the murine T-cell antigen receptor beta chains were measured for all possible V beta-J beta combinations. This analysis shows that bet...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.9.4319

    authors: Pannetier C,Cochet M,Darche S,Casrouge A,Zöller M,Kourilsky P

    更新日期:1993-05-01 00:00:00

  • Economic repercussions of fisheries-induced evolution.

    abstract::Fish stocks experiencing high fishing mortality show a tendency to mature earlier and at a smaller size, which may have a genetic component and therefore long-lasting economic and biological effects. To date, the economic effects of such ecoevolutionary dynamics have not been empirically investigated. Using 70 y of da...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1212593110

    authors: Eikeset AM,Richter A,Dunlop ES,Dieckmann U,Stenseth NC

    更新日期:2013-07-23 00:00:00

  • Novel sensory adaptation mechanism in bacterial chemotaxis to oxygen and phosphotransferase substrates.

    abstract::The involvement of methylation in the chemosensory response of bacteria to many attractants has been clearly established by studies in several laboratories. It has been assumed that adaptation of Salmonella typhimurium and Escherichia coli to all attractants involves methylation of a transmembrane methyl-accepting che...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.1.11

    authors: Niwano M,Taylor BL

    更新日期:1982-01-01 00:00:00

  • The endoplasmic reticulum-sarcoplasmic reticulum connection: distribution of endoplasmic reticulum markers in the sarcoplasmic reticulum of skeletal muscle fibers.

    abstract::The skeletal muscle sarcoplasmic reticulum (SR) was investigated for the presence of well-known endoplasmic reticulum (ER) markers: the lumenal protein BiP and a group of membrane proteins recognized by an antibody raised against ER membrane vesicles. Western blots of SR fractions revealed the presence of BiP in fast-...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.13.6142

    authors: Volpe P,Villa A,Podini P,Martini A,Nori A,Panzeri MC,Meldolesi J

    更新日期:1992-07-01 00:00:00

  • Soluble factors from T cells inhibiting X4 strains of HIV are a mixture of β chemokines and RNases.

    abstract::T-cell-derived soluble factors that inhibit both X4 and R5 HIV are recognized as important in controlling HIV. Whereas three β chemokines, regulated-on-activation normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1α, and MIP-1β, account for the suppression of R5 HIV by blockade of HI...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1202240109

    authors: Cocchi F,DeVico AL,Lu W,Popovic M,Latinovic O,Sajadi MM,Redfield RR,Lafferty MK,Galli M,Garzino-Demo A,Gallo RC

    更新日期:2012-04-03 00:00:00

  • Binding to selected regions of reovirus mRNAs by a nonstructural reovirus protein.

    abstract::When assembled into 13--19S particles, the reovirus nonstructural protein sigma-NS selectively binds single-stranded RNAs. Sedimentation analyses combined with binding to nitrocellulose membrane filters showed that 1--2 pmol of reovirus mRNAs from the large, medium, or small size classes saturated in vitro the binding...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.11.3457

    authors: Stamatos NM,Gomatos PJ

    更新日期:1982-06-01 00:00:00

  • IL-38 inhibits microglial inflammatory mediators and is decreased in amygdala of children with autism spectrum disorder.

    abstract::Autism spectrum disorder (ASD) is characterized by impaired social interactions and communication. The pathogenesis of ASD is not known, but it involves activation of microglia. We had shown that the peptide neurotensin (NT) is increased in the serum of children with ASD and stimulates cultured adult human microglia t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2004666117

    authors: Tsilioni I,Pantazopoulos H,Conti P,Leeman SE,Theoharides TC

    更新日期:2020-07-14 00:00:00

  • Spatial embedding of structural similarity in the cerebral cortex.

    abstract::Recent anatomical tracing studies have yielded substantial amounts of data on the areal connectivity underlying distributed processing in cortex, yet the fundamental principles that govern the large-scale organization of cortex remain unknown. Here we show that functional similarity between areas as defined by the pat...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1414153111

    authors: Song HF,Kennedy H,Wang XJ

    更新日期:2014-11-18 00:00:00

  • Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior.

    abstract::The acid-sensing ion channel 1a (ASIC1a) is abundantly expressed in the amygdala complex and other brain regions associated with fear. Studies of mice with a disrupted ASIC1 gene suggested that ASIC1a may contribute to learned fear. To test this hypothesis, we generated mice overexpressing human ASIC1a by using the pa...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0308753101

    authors: Wemmie JA,Coryell MW,Askwith CC,Lamani E,Leonard AS,Sigmund CD,Welsh MJ

    更新日期:2004-03-09 00:00:00

  • Demonstration of globin messenger sequences in giant nuclear precursors of messenger RNA of avian erythroblasts.

    abstract::Highly purified globin mRNA from ducks was copied with RNA-directed DNA polymerase from avian myeloblastosis virus into anti-messenger DNA. With excess RNA, more than 90% of this DNA annealed back to its template with a C(o)t/2 value of 7.5 x 10(-4) mol.sec. liter(-1); the melting temperature of the hybrid was 86 degr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.70.4.1122

    authors: Imaizumi T,Diggelmann H,Scherrer K

    更新日期:1973-04-01 00:00:00

  • Sonic Hedgehog promotes the development of multipotent neural crest progenitors endowed with both mesenchymal and neural potentials.

    abstract::In the vertebrate embryo, the cephalic neural crest cells (CNCCs) produce cells belonging to two main lineages: the neural [including neurons, glial cells of the peripheral nervous system (PNS), and melanocytes] and the mesenchymal (chondrocytes, osteoblasts, smooth muscle cells, and connective tissue cells), whereas ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0708806104

    authors: Calloni GW,Glavieux-Pardanaud C,Le Douarin NM,Dupin E

    更新日期:2007-12-11 00:00:00

  • Valinomycin-induced uptake of potassium in membrane vesicles from Escherichia coli.

    abstract::Osmotically shocked Escherichia coli and membrane vesicle ghosts from E. coli cells have lost the ability to accumulate potassium by active transport. The addition of valinomycin to the membrane ghosts restores the capacity to accumulate radioactive (42)K and (86)Rb by a temperature- and energy-dependent process. Memb...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.68.7.1488

    authors: Bhattacharyya P,Epstein W,Silver S

    更新日期:1971-07-01 00:00:00

  • Stem cells are dispensable for lung homeostasis but restore airways after injury.

    abstract::Local tissue stem cells have been described in airways of the lung but their contribution to normal epithelial maintenance is currently unknown. We therefore developed aggregation chimera mice and a whole-lung imaging method to determine the relative contributions of progenitor (Clara) and bronchiolar stem cells to ep...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0900668106

    authors: Giangreco A,Arwert EN,Rosewell IR,Snyder J,Watt FM,Stripp BR

    更新日期:2009-06-09 00:00:00

  • Co-occupancy by multiple cardiac transcription factors identifies transcriptional enhancers active in heart.

    abstract::Identification of genomic regions that control tissue-specific gene expression is currently problematic. ChIP and high-throughput sequencing (ChIP-seq) of enhancer-associated proteins such as p300 identifies some but not all enhancers active in a tissue. Here we show that co-occupancy of a chromatin region by multiple...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1016959108

    authors: He A,Kong SW,Ma Q,Pu WT

    更新日期:2011-04-05 00:00:00

  • BCR/ABL inhibition by an escort/phosphatase fusion protein.

    abstract::Cellular transformation by the BCR/ABL oncogene depends on the ABL-encoded tyrosine kinase activity. To block BCR/ABL function, we created a unique tyrosine phosphatase by fusing the catalytic domain of SHP1 (SHP1c) to the ABL binding domain (ABD) of RIN1, an established binding partner and substrate for c-ABL and BCR...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.210253497

    authors: Lim YM,Wong S,Lau G,Witte ON,Colicelli J

    更新日期:2000-10-24 00:00:00

  • Molecular cloning of a DNA sequence complementary to creatine kinase M mRNA from chickens.

    abstract::We have cloned and identified a DNA sequence complementary to the mRNA of creatine kinase (CK) isozyme M, although the mRNA is a minor species of the total mRNA in developing myoblasts. Poly(A)+RNA from breast and thigh muscle of 5-week-old chicks was enriched for CK mRNA by a novel procedure of sucrose gradient centr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.16.4997

    authors: Schweinfest CW,Kwiatkowski RW,Dottin RP

    更新日期:1982-08-01 00:00:00

  • Cytokine Diedel and a viral homologue suppress the IMD pathway in Drosophila.

    abstract::Viruses are obligatory intracellular parasites that suffer strong evolutionary pressure from the host immune system. Rapidly evolving viral genomes can adapt to this pressure by acquiring genes that counteract host defense mechanisms. For example, many vertebrate DNA viruses have hijacked cellular genes encoding cytok...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1516122113

    authors: Lamiable O,Kellenberger C,Kemp C,Troxler L,Pelte N,Boutros M,Marques JT,Daeffler L,Hoffmann JA,Roussel A,Imler JL

    更新日期:2016-01-19 00:00:00

  • Induction of c-sis mRNA and activity similar to platelet-derived growth factor by transforming growth factor beta: a proposed model for indirect mitogenesis involving autocrine activity.

    abstract::Treatment of quiescent cultures of mouse embryo-derived AKR-2B cells with transforming growth factor beta resulted in an early induction of c-sis mRNA. The increase in c-sis mRNA was followed by a corresponding increase in protein similar to platelet-derived growth factor (PDGF) in the culture medium. In addition, PDG...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.8.2453

    authors: Leof EB,Proper JA,Goustin AS,Shipley GD,DiCorleto PE,Moses HL

    更新日期:1986-04-01 00:00:00

  • Species-fragmented area relationship.

    abstract::The species-area relationship (SAR) gives a quantitative description of the increasing number of species in a community with increasing area of habitat. In conservation, SARs have been used to predict the number of extinctions when the area of habitat is reduced. Such predictions are most needed for landscapes rather ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1311491110

    authors: Hanski I,Zurita GA,Bellocq MI,Rybicki J

    更新日期:2013-07-30 00:00:00

  • Cholesterol increases kinetic, energetic, and mechanical stability of the human β2-adrenergic receptor.

    abstract::The steroid cholesterol is an essential component of eukaryotic membranes, and it functionally modulates membrane proteins, including G protein-coupled receptors. To reveal insight into how cholesterol modulates G protein-coupled receptors, we have used dynamic single-molecule force spectroscopy to quantify the mechan...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1210373109

    authors: Zocher M,Zhang C,Rasmussen SG,Kobilka BK,Müller DJ

    更新日期:2012-12-11 00:00:00

  • Nascent RNA structure modulates the transcriptional dynamics of RNA polymerases.

    abstract::RNA polymerase pausing represents an important mechanism of transcriptional regulation. In this study, we use a single-molecule transcription assay to investigate the effect of template base-pair composition on pausing by RNA polymerase II and the evolutionarily distinct mitochondrial polymerase Rpo41. For both enzyme...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1205063109

    authors: Zamft B,Bintu L,Ishibashi T,Bustamante C

    更新日期:2012-06-05 00:00:00