Processing

Please wait...

Settings

Settings

Goto Application

1. WO2008045120 - TRANSGENIC MOUSE LINES EXPRESSING HUMAN ACE2 AND USES THEREOF

Publication Number WO/2008/045120
Publication Date 17.04.2008
International Application No. PCT/US2007/000744
International Filing Date 11.01.2007
IPC
C12N 15/00 2006.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
G01N 33/00 2006.01
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
A01K 67/027 2006.01
AHUMAN NECESSITIES
01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
67Rearing or breeding animals, not otherwise provided for; New breeds of animals
027New breeds of vertebrates
CPC
A01K 2217/05
AHUMAN NECESSITIES
01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
2217Genetically modified animals
05Animals comprising random inserted nucleic acids (transgenic)
A01K 2227/105
AHUMAN NECESSITIES
01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
2227Animals characterised by species
10Mammal
105Murine
A01K 2267/0337
AHUMAN NECESSITIES
01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
2267Animals characterised by purpose
03Animal model, e.g. for test or diseases
0337Animal models for infectious diseases
A01K 67/0275
AHUMAN NECESSITIES
01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
67Rearing or breeding animals, not otherwise provided for; New breeds of animals
027New breeds of vertebrates
0275Genetically modified vertebrates, e.g. transgenic
C12N 15/8509
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09Recombinant DNA-technology
63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
79Vectors or expression systems specially adapted for eukaryotic hosts
85for animal cells
8509for producing genetically modified animals, e.g. transgenic
C12N 9/48
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
9Enzymes; Proenzymes; Compositions thereof
14Hydrolases (3)
48acting on peptide bonds (3.4)
Applicants
  • THE BOARD OF TRUSTEES OF THE UNIVERSITY OF TEXAS SYSTEM AND CHAN ET AL [US]/[US] (AllExceptUS)
  • CHAN, Teh-Sheng [US]/[US] (UsOnly)
  • PETERS, Clarence, J. [US]/[US] (UsOnly)
  • TSENG, Chien-Te, K. [US]/[US] (UsOnly)
  • MAKINO, Shinji [JP]/[US] (UsOnly)
Inventors
  • CHAN, Teh-Sheng
  • PETERS, Clarence, J.
  • TSENG, Chien-Te, K.
  • MAKINO, Shinji
Agents
  • ADLER, Benjamin, A.
Priority Data
60/758,18911.01.2006US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) TRANSGENIC MOUSE LINES EXPRESSING HUMAN ACE2 AND USES THEREOF
(FR) LIGNÉES DE SOURIS TRANSGÉNIQUES EXPRIMANT L'ACE2 HUMAINE ET LEURS UTILISATIONS
Abstract
(EN)
Animal models for severe acute respiratory syndrome (SARS)-coronavirus infection of humans are needed to elucidate SARS pathogenesis and develop vaccines and antivirals. Transgenic mice were developed expressing human angiotensin-converting enzyme 2, a functional receptor for the virus, under the regulation of a global promoter. A transgenic lineage, designated AC70, was among the best characterized against SARS coronavirus infection, showing weight loss and other clinical manifestations before reaching 100% mortality within 8 days after intranasal infection. High virus titers were detected in the lungs and brains of transgene-positive mice on days 1 and 3 after infection. Inflammatory mediators were also detected in these tissues, coinciding with high levels of virus replication. In contrast, infected transgene-negative mice survived without showing any clinical illness. The severity of the disease developed in these transgenic mice, AC70 in particular, makes these mouse models valuable not only for evaluating the efficacy of antivirals and vaccines, but also for studying SARS coronavirus pathogenesis and infection by other coronaviruses utilizing human ACE2 for viral entry into cells.
(FR)
La présente invention concerne des modèles animaux portant sur les infections à coronavirus tel le syndrome respiratoire aigu sévère (SRAS) chez les hommes, qui permettraient de résoudre la pathogenèse du SRAS et de développer des vaccins et des antiviraux. Les souris transgéniques ont été développées de manière à exprimer l'enzyme 2 convertissant l'angiotensine humaine, un récepteur fonctionnel du virus, sous la régulation d'un promoteur global. Une lignée transgénique, nommée AC70, était parmi les mieux caractérisées par rapport à l'infection à coronavirus du SRAS, en présentant une perte de poids et d'autres manifestations cliniques avant d'atteindre 100 % de mortalité dans les 8 jours suivant l'infection intranasale. Des titres viraux élevés ont été détectés dans les poumons et le cerveau de souris transgéniques positives les jours 1 et 3 après l'infection. Des médiateurs inflammatoires ont également été détectés dans ces tissus, coïncidant ainsi avec des niveaux élevés de réplication du virus. En revanche, les souris transgéniques négatives infectées ont survécu sans présenter aucune maladie clinique. La gravité de la maladie développée dans ces souris transgéniques, en particulier les AC70, donnent à ces modèles de souris une grande valeur non seulement pour évaluer l'efficacité d'antiviraux et de vaccins, mais également pour étudier la pathogenèse du coronavirus du SRAS et les infections induites par d'autres coronavirus utilisant l'ACE2 humain pour effectuer une entrée virale dans les cellules.
Also published as
Latest bibliographic data on file with the International Bureau