Central Institute for Experimental Animals (Japan)
Inventor
Yurimoto, Terumi
Seki, Fumiko
Sasaki, Erika
Inoue, Takashi
Abstract
The invention provides a bed that enables non-invasive functional MRI for general purposes. The invention provides a functional MRI bed system equipped with a helmet to immobilize the head of the animal with a U-shaped fixture.
A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
2.
GENETICALLY MODIFIED EXPERIMENTAL ANIMAL PRODUCTION METHOD BY WHICH MOSAIC MODIFICATION IS REDUCED OR AVOIDED
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
Inventor
Kumita Wakako
Sasaki Erika
Kurotaki Yoko
Abstract
Provided is a genetically modified experimental animal production method by which a mosaic modification is reduced or avoided when producing a genetically modified experimental animal. This method for reducing the frequency at which mosaic modified embryos are produced when modifying genes of fertilized eggs or embryos of vertebrates by a genetic modification technology comprises injecting a genetic modification tool into fertilized eggs or embryos and then dividing embryos of 2-32 cell stages to produce embryos composed of one or more blastomeres.
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
Inventor
Kametani Yoshie
Ito Ryoji
Abstract
Provided is a tumor-bearing immune nonhuman animal that enables suppression of the onset of graft-versus-host disease (GVHD) and engraftment of T cells and/or B cells. Human peripheral blood monocytes are transplanted into a tumor-bearing immunodeficient nonhuman animal based on an immunodeficient nonhuman animal into which human IL-4 gene has been introduced.
A01K 67/027 - New or modified breeds of vertebrates
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
C12N 5/078 - Cells from blood or from the immune system
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
Inventor
Yurimoto Terumi
Inoue Takashi
Sasaki Erika
Iriki Atsushi
Yamazaki Yumiko
Abstract
An analysis assistance device comprising an individual tracking unit that, for a target animal to be analyzed, acquires behavior history information individually indicating a behavior history of the target animal on the basis of at least one of: image information acquired by an image sensor acquiring an image of the target animal; acoustic information acquired by an acoustic sensor acquiring sound produced by the target animal; information acquired by a wearable sensor worn by the target animal; and information acquired from terminal information.
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
Inventor
Yurimoto Terumi
Seki Fumiko
Sasaki Erika
Inoue Takashi
Abstract
Provided is a bed that enables noninvasive and multipurpose functional MRI imaging. Provided is a bed system for functional MRI, the bed system having a helmet for immobilizing the head of an animal using a U-shaped appliance.
A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
G01N 24/00 - Investigating or analysing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
6.
EXCREMENT PROPERTY ESTIMATION MODEL TRAINING DEVICE, EXCREMENT PROPERTY ESTIMATION DEVICE, EXCREMENT PROPERTY ESTIMATION MODEL TRAINING METHOD, EXCREMENT PROPERTY ESTIMATION METHOD, AND PROGRAM
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
Inventor
Yurimoto Terumi
Sasaki Erika
Inoue Takashi
Abstract
Provided is an excrement property estimation model training device comprising: an excrement space which is a predetermined space where there is excrement from an animal being reared; a training data acquisition unit that acquires training data including input-side training data including training image data of a captured result image in which the excrement space is captured, and correct labels indicating whether any abnormal excrement is reflected in the image shown in the training image data; an excrement property estimation training model execution unit that uses an excrement property estimation training model, which is a machine learning model for estimating the probability of abnormal excrement being reflected in the training image data, to estimate the probability of abnormal excrement being reflected in the image shown in the training image data; and an update unit that, on the basis of differences between estimation results from the excrement property estimation training model execution unit and the correct labels, updates the excrement property estimation training model such that the differences are reduced.
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
Inventor
Ito Ryoji
Abstract
The purpose of the present invention is to provide: a method for creating a humanized rodent model in which a functional human immune system is reconstructed as a result of differentiating human dendritic cells; and said rodent model. Provided is an immunodeficient rodent in which the human FLT3L gene is transgenically introduced and in which the FLT3 gene that the rodent originally had has been knocked out.
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
Inventor
Ito, Ryoji
Abstract
An object of the present invention is to provide a humanized mouse in which human hematopoietic stem cells can be engrafted for a long term. The present invention relates to a humanized rodent having human neutrophils circulating in a periphery, obtained by transplanting a human hematopoietic stem cell into a human G-CSF gene knock-in rodent, which is an immunodeficient rodent deficient in a G-CSF receptor function by knock-in of a human G-CSF gene at a G-CSF receptor locus, wherein a human G-CSF is expressed and a rodent G-CSF receptor is not expressed.
Central Institute for Experimental Animals (Japan)
Inventor
Takahashi, Takeshi
Katano, Ikumi
Abstract
An object of the present invention is to provide an immunodeficient mouse which is capable of eliminating effects of immune cells from the immunodeficient mouse against human antibodies and in which human cells are engrafted at high level.
Deletion of a mouse FcgR gene from an NOG mouse results in a mouse that does not exhibit antibody-dependent cellular cytotoxic activity on tumors, and in the mouse, human cells can be engrafted at significantly higher level than that in the NOG mouse. Furthermore, by introducing the human IL-15 gene into the mouse and engrafting a human NK cell in the mouse, only human NK cells become effector cells to enable evaluation of ADCC activity.
Central Institute for Experimental Animals (Japan)
Inventor
Suemizu, Hiroshi
Abstract
This invention provides a non-human vertebrate exhibiting a higher human liver cell growth rate, a higher human liver cell replacement rate, and higher histological-physiological human reproducibility than existing non-human vertebrates comprising the human liver transplanted therein and a method for producing such non-human vertebrate. Specifically, the method for producing a transgenic non-human vertebrate comprising human liver cells transplanted therein comprises transplanting human liver cells in a non-human vertebrate that has impaired or lowered immune reactions against humans in the presence of human IL-6 in vivo.
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
HIROSHIMA UNIVERSITY (Japan)
Inventor
Sasaki, Erika
Sato, Kenya
Kumita, Wakako
Sasaguri, Hiroki
Saido, Takaomi
Nagata, Kenichi
Yamamoto, Takashi
Sakuma, Tetsushi
Abstract
Provided is an animal model that can reproduce the pathological conditions of human AD. A region associated with the splicing of exon 9 of the PSEN1 gene is deleted in the non-human primate Alzheimer's disease model.
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
Inventor
Ito Ryoji
Abstract
The purpose of the present invention is to provide a humanized mouse that enables the long-term survival of human hematopoietic stem cells. The present invention is a humanized rodent in which human neutrophils circulate peripherally, and is obtained by transplanting human hematopoietic cells into a human G-CSF gene knocked-in rodent that expresses human G-CSF and does not express rodent G-CSF receptor. The human G-CSF gene knocked-in rodent is an immunodeficient rodent in which a human G-CSF gene has been knocked into the G-CSF receptor gene locus and the function of the G-CSF receptor has been lost.
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
THE BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA (USA)
Inventor
Poluektova Larisa
Gorantla Santhi
Ito Mamoru
Katano Ikumi
Abstract
The present invention provides a non-human animal having inside the body thereof human interleukin 34 (IL-34). The present invention also provides a method for producing a non-human animal having human microglia, the method including transplanting human CD34 positive hematopoietic cells into the non-human animal. The present invention also provides a method for manufacturing the human microglia, the method including obtaining the human microglia from the non-human animal having the human microglia.
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
Inventor
Suemizu Hiroshi
Takahashi Takeshi
Abstract
Provided are: a non-human vertebrate that shows a higher growth speed of human hepatocytes, a higher substitution rate of the human hepatocytes and better histological and physiological human remodeling properties compared with conventional non-human vertebrates transplanted with human hepatocytes; and a method for producing the same. A method for producing a transgenic non-human vertebrate transplanted with human hepatocytes, said method comprising transplanting a non-human vertebrate, in which immune response to humans is deficient or depressed, with human hepatocytes in a state where human IL-6 is present in vivo.
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
Inventor
Takahashi, Takeshi
Katano, Ikumi
Abstract
The present invention addresses the problem of providing an immunodeficient mouse that is capable of excluding the influence of immunodeficient mouse-derived immune cells on human antibodies and has high engraftment of human cells. When a mouse FcgR gene is additionally deleted from a NOG mouse, the mouse does not express antibody-dependent cytotoxicity activity to tumors, and human cells are engrafted at a significantly higher rate compared to a NOG mouse. Furthermore, by engrafting human NK cells to the mouse that is introduced with a human IL-15 gene, only the human NK cells become effector cells, and ADCC activity can be evaluated.
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
Inventor
Okamoto, Kazuya
Nagai, Daichi
Ito, Mamoru
Ito, Ryoji
Abstract
Provided are: a method for evaluating the hematological toxicity of a drug under evaluation, said method showing an excellent clinical predictability of bone marrow toxicity; and a model for evaluating the hematological toxicity of a drug under evaluation. The method for evaluating the hematological toxicity of a drug under evaluation comprises: a step for administering the drug under evaluation to a humanized modified NOG mouse, said NOG mouse having been constructed by transferring human GM-CSF/IL-3 gene into an NOG mouse and containing 20 % by number or more of leucocytes from human in leucocytes in the blood; and a step for counting the leucocytes from human in a sample from the modified NOG mouse, to which the drug under evaluation has been administered, and, when the number of the leucocytes from human changes compared with a sample of a control to which a vehicle has been administered as a substitute for the drug under evaluation, then evaluating the drug under evaluation as having hematological toxicity.
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
Inventor
Ito, Mamoru
Katano, Ikumi
Abstract
The present invention addresses the problem of providing a mouse by using which the function of human NK cells can be examined. An NOD-scid,IL-2rγnull-hIL-15 Tg mouse that is prepared by inserting DNA comprising a base sequence represented by SEQ ID NO:1, said base sequence being a gene region containing DNA wherein a cDNA sequence encoding interleukin 15 (IL-15) is operably linked to a cDNA sequence encoding the signal peptide of human interleukin 2 (IL-2), into cDNA of an immunodeficient mouse. From this mouse, hCD56+ cells can be detected at a concentration sufficient for studying in vivo mature human NK cells at least for 6 months after the transplantation.
Central Institute for Experimental Animals (Japan)
Keio University (Japan)
Inventor
Sasaki, Erika
Okano, Hideyuki
Abstract
An object of the present invention is to provide a method for introducing a gene into an embryo for production of a human disease model primate animal using a non-human primate animal such as a marmoset. The present invention relates to a method for introducing a foreign gene into an early embryo of a non-human primate animal, which comprises placing early embryos of a non-human primate in a 0.2 M to 0.3 M sucrose solution, so as to increase the volume of the perivitelline spaces, and then injecting a viral vector containing a human foreign gene operably linked to a promoter into the perivitelline spaces of the early embryos.
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
CHUGAI SEIYAKU KABUSHIKI KAISHA (Japan)
Inventor
Suemizu, Hiroshi
Kawai, Kenji
Nakamura, Masato
Hasegawa, Masami
Abstract
Disclosed is a mouse having human hepatocytes transplanted therein. Specifically disclosed is a mouse having human hepatocytes transplanted therein. In the mouse, a foreign thymidine kinase gene or an urokinase-type plasminogen activator gene is retained so that the gene can be expressed specifically in the liver of the mouse, and hepatocytes of the mouse are substituted by human hepatocytes.
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
21.
METHOD FOR INTRODUCING FOREIGN GENE INTO EARLY EMBRYO OF PRIMATE ANIMAL, AND METHOD FOR PRODUCTION OF TRANSGENIC PRIMATE ANIMAL COMPRISING THE INTRODUCTION METHOD
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
KEIO UNIVERSITY (Japan)
Inventor
Sasaki, Erika
Okano, Hideyuki
Abstract
The object is to provide a method for introducing a gene into an embryo for the purpose of producing a human disease model primate animal by using a non-human primate animal such as a marmoset. Disclosed is a method for introducing a foreign gene into an early embryo of a non-human primate animal, which comprises the steps of: placing the early embryo of the non-human primate animal in a 0.2-0.3 M sucrose solution to increase the volume of a perivitelline space of the early embryo; and injecting a viral vector carrying a human foreign gene operably linked to a promoter into the perivitelline space of the early embryo.
Central Institute for Experimental Animals (Japan)
Inventor
Eto, Tomoo
Sasaki, Erika
Abstract
This invention provides a solution for preserving mammalian early embryos or ES cells by vitrification, which comprises, as a base material, a phosphate buffer that exclusively contains 10% to 15% (v/v) propylene glycol as polyhydric alcohol or a phosphate buffer that exclusively contains 10% to 15% (v/v) propylene glycol and 25% to 35% (v/v) ethylene glycol as polyhydric alcohols and further contains 15% to 25% (v/v) Percoll® and 0.2 M to 0.5 M sucrose. This invention also provides a method for preserving mammalian early embryos or ES cells by vitrification using such solution.
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
TOHOKU UNIVERSITY (Japan)
Inventor
Kitamoto, Tetsuyuki
Kobayashi, Atsushi
Asano, Masahiro
Abstract
It is intended to design a prion protein molecule, which is easily converted into an abnormal prion, by transferring a point mutation into a prion protein. Namely, a method of designing a prion protein having an amino acid substitution, whereby the conversion ability of a prion protein from a normal type into an abnormal type is promoted, which comprises: constructing mutant prion proteins comprising a plural number of prion proteins having been subjected to comprehensive amino acid substitutions in a prion protein, measuring the conversion ability of these mutant prion proteins from a normal type into an abnormal type, and selecting a mutant prion protein having a promoted conversion ability of a prion protein from a normal type into an abnormal type compared with the wild type prion protein.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
A01K 67/027 - New or modified breeds of vertebrates
CENTRAL INSTITUTE FOR EXPERIMENTAL ANIMALS (Japan)
Inventor
Maruyama, Tetsuo
Masuda, Hirotaka
Yoshimura, Yasunori
Okano, Hideyuki
Okano, James Hirotaka
Matsuzaki, Yumi
Abstract
It is intended to provide an animal model which can reflect a lesion site of human endometriosis more faithfully, a method for producing the same, an animal model which enables noninvasive observation of a transplanted cell, and a method for producing the same. The animal model which has a uniform endometriosis lesion can be produced by introducing an expression vector containing a gene encoding an observation marker such as luciferase into a cell isolated from human, transplanting a cell which has come to express the observation marker under the renal capsule of an immunodeficient mouse such as an NOG mouse, and isolating the cell to be transplanted from the endometrium or a focal site of endometriosis.
