287 results about "Knockout animal" patented technology

The present invention relates to a method for screening therapeutic drugs of schizophrenia using an animal model of the disease. More specifically, this invention relates to a screening method based on the phospholipase C β1 (PLCβ1) knockout mouse as an animal model of schizophrenia with all the major symptoms of the human disease. This knockout mouse exhibits symptoms similar to human schizophrenia such as locomotor hyperactivity, impaired prepulse inhibition of the startle response, lack of barbering and nesting behaviors, socially subordinate status, impaired learning, and lack of type II theta rhythm which has been implicated in working memory. Thus, the knockout mouse of the present invention can be useful as an animal for screening therapeutic drugs against schizophrenia.

A viable global NaV1.7− / − knockout mouse is disclosed, and a breeding colony of global NaV1.7− / − knockout mice. Also disclosed are an isolated mouse gamete that does not encode a functional NaV1.7− / −, produced by the NaV1.7− / − knockout mouse; an isolated NaV1.7− / − mouse cell, or a progeny cell thereof, isolated from the NaV1.7− / − knockout mouse; and a primary cell culture or a secondary cell line and a tissue or organ explant or culture thereof derived from the NaV1.7− / − knockout mouse. Disclosed also are a hybridoma, wherein the hybridoma was originally formed from the fusion of the isolated NaV1.7− / − mouse cell mouse cell and a myeloma cell, and a method of making an antibody. Also disclosed are assays useful for screening prospective NaV1.7 inhibitors and dose ranging a test NaV17 inhibitor compound, which were validated using the NaV1.7− / − knockout mouse.

The present invention provides an immunodeficient mouse (NOG mouse) suitable for engraftment, differentiation and proliferation of heterologous cells, and a method of producing such a mouse. This mouse is obtained by backcrossing a C.B-17-scid mouse with an NOD / Shi mouse, and further backcrossing an interleukin 2-receptor γ-chain gene-knockout mouse with the thus backcrossed mouse. It is usable for producing a human antibody and establishing a stem cell assay system, a tumor model and a virus-infection model.

This invention provides a therapeutic agent for inhibiting neovascularization, a therapeutic agent for a solid cancer, a therapeutic agent for a disease pathologically caused by neovascularization, and a therapeutic agent for repairing a tissue comprising as the effective ingredient, a substance that potentiates the action of CXCR4.Based on the finding that vascularization is suppressed in CXCR4 knockout mice, it becomes possible to prepare a therapeutic agent for suppressing vascularization, a therapeutic agent for a solid cancer, a therapeutic agent for a disease pathologically caused by neovascularization, each of which comprises as the effective ingredient, a substance that inhibits the action of CXCR4, as well as to prepare a therapeutic agent for repairing a tissue comprising as the effective ingredient, a substance that potentiates the action of CXCR4. Methods for treatment are made possible that use these therapeutic agents.

Disclosed herein are methods for generating recombinant DNA molecules in cells using homologous recombination mediated by recombinases and similar proteins. The methods promote high efficiency homologous recombination in bacterial cells, and in eukaryotic cells such as mammalian cells. The methods are useful for cloning, the generation of transgenic and knockout animals, and gene replacement. The methods are also useful for subcloning large DNA fragments without the need for restriction enzymes. The methods are also useful for repairing single or multiple base mutations to wild type or creating specific mutations in the genome. Also disclosed are bacterial strains and vectors which are useful for high-efficiency homologous recombination.

The disclosure concerns a method for resistance of epilepsy by suppressing the function of alpha 1 G protein of T-type calcium channels, use of suppressor of alpha 1 G protein for prevention or treatment for epilepsy, knockout mice resisting epilepsy by disrupting alpha 1 G subunit of T-type calcium channel, and preparation method thereof. In addition, suppressing alpha 1 G protein of T-type calcium channels does not occur epilepsy, and alpha 1 G-deficient mice are useful to study of mechanism related to epilepsy.

The present invention provides an immunodeficient mouse (NOG mouse) suitable for engraftment, differentiation and proliferation of heterologous cells, and a method of producing such a mouse. This mouse is obtained by backcrossing a C.B-17-scid mouse with an NOD / Shi mouse, and further backcrossing an interleukin 2-receptor γ-chain gene-knockout mouse with the thus backcrossed mouse. It is usable for producing a human antibody and establishing a stem cell assay system, a tumor model and a virus-infection model.

The disclosure concerns a method for resistance of epilepsy by suppressing the function of alpha 1G protein of T-type calcium channels, use of suppressor of alpha 1G protein for prevention or treatment for epilepsy, knockout mice resisting epilepsy by disrupting alpha 1G subunit of T-type calcium channel, and preparation method thereof. The α1G-knockout transgenic mouse can be used for investigating the relationship between diseases particularly neuropathy or psychopathy and the function of α1G T-type calcium channel via various behavioral tests since α1G subunit is mainly expression in central nervous system (CNS) and pheripheral nervous system (PNS). Further, the α1G-knockout transgenic mouse can be used for screening antileptic agents.

The invention discloses a construction method for a mouse model with conditionally deleted Tmem30a genes and with pancreatic beta cells and an application. The construction method comprises the following steps: constructing a conditionally deleted Tmem30a gene homozygote mouse, wherein the two ends of one or more exon of the Tmem30a genes are inserted into homonymous arrayed loxP locus; mating the mouse with pancreatic beta cell specific transgenic mouse Ins2-Cre, thereby acquiring the mouse model with conditionally deleted Tmem30a genes and with pancreatic beta cells. The mouse with conditionally deleted Tmem30a genes and with pancreatic beta cells shows glucose intolerance and poor insulin sensitivity. The mouse model can be used as a diabetes research model.

By means of a proteomic approach, the markers of hepatocellular carcinoma (HCC) in the liver of a knockout mouse (MAT1A- / -) have been identified for the MAT1A gene (deficient in the synthesis of S-adenosylmethionine). 27 proteins have been detected the expression thereof is altered in, at least, 50% of the analysed tumours. Amongst them, 13 proteins have been validated in biopsies of patients with HCC of different etiology, and 7 of them have been validated in biopsies of patients with liver cirrhosis, a stage prior to the development of HCC, which makes it possible to differentiate between prior stages of the disease and even between different etiologies (viral and alcoholic). Having a panel of markers available may contribute to more accurately defining the alterations associated with the development of HCC and thus facilitate prognosis and diagnosis of this disease.

Methods and compositions for use in treating anxiety are provided. In the subject methods, an effective amount of an agent having ApoE3 activity is administered to a host suffering from an anxiety, e.g. excessive anxiety, unwanted anxiety, an anxiety disorder, etc. Also provided are methods and compositions for modulating adrenal steroidogenesis and / or release, particularly stress induced adrenal steroidogenesis and / or release, and the hippocampal-pituitary-adrenal (HPA) axis. In these methods, an effective amount of an ApoE activity modulating agent, e.g. an ApoE agonist or antagonist, is administered to the host.

An animal model of coronary heart disease has been developed where myocardial infarct can be induced by altering the animal's diet. In all embodiments, this animal model is a result of reduced activity of scavenger receptor class BI (SR-BI) and apolipoprotein E (ApoE). In a preferred embodiment, the model is a result of crossbreeding two transgenic mouse lines: a knockout of SR-BI (SR-BI− / −) and an impaired ApoE expressor (hypoE). The impaired ApoE gene results in only 2-5% expression of ApoE and a reduction in cholesterol homeostasis. Resulting animals are predisposed to hypercholesterolemia but can live longer than a year on a normal low fat diet. Serum plasma levels can be significantly elevated by changing the animal's diet to one containing high levels of fat and cholesterol. Within a month on a high fat, high cholesterol diet, animals develop atherosclerosis and myocardial infarction occurs. Survival depends on the nature of the diet and the conditions of animal husbandry and can typically be around 20-30 days after administration of the modified diet depending on the specific conditions. Housing the animals alone or in groups significantly affects survival of these animals on a high fat diet. Analysis of B- and T-cell deficient SR-BI / ApoE / RAG2 triple knockout mice established that B- and T-lymphocytes do not play a key role in the pathophysiology of the SR-BI ApoE dKO model of human disease. These animal models can be used to study mechanisms and progression of CHD as a function of diet, treatment with drugs to be screened for efficacy or undesirable side effects, and social environmental effects.

Methods for testing candidate drugs for treatment of age-related macular degeneration are provided. Ccl2-deficient, and Ccr2-deficient mice are used to determine the effect of candidate drugs and treatments on development of age-related macular degeneration. Also provided is a Ccl2-deficient, Ccr2-deficient dual knockout mouse, which is a useful animal model for age-related macular degeneration.

The invention discloses novel application of a human YTHDF1 (Youth-Tech-Health Domain Family Member 1) gene, that is, a human YTHDF1 gene expression amount detection reagent is applied to preparationof lung cancer clinical diagnosis reagents, a human YTHDF1 gene is applied to preparation of lung cancer medicines, compared with normal pulmonary epithelial cells, the YTHDF1 gene is highly expressed in lung cancer cells, RNA (Ribonucleic Acid) designed according to the YTHDF1 gene is capable of interfering slow viruses, inhibiting expression of YTHDF1, remarkably inhibiting proliferation of thelung cancer cells, retarding tumor cell division at a G0 / G1 phase and promoting cell apoptosis, inhibiting formation of nude mouse transplanted tumour, and furthermore the purpose of treating lung cancer can be achieved; YTHDF1 gene knockout mouse tumor formation capability detection shows that cell proliferation is remarkably inhibited, and cell apoptosis is remarkably increased; the results show that the YTHDF1 gene can be used as a target for lung cancer treatment, and wide prospects are provided for development of lung cancer treatment medicines based on YTHDF1 genes in future.

The present invention provides a method of producing pluripotent stem cells, which comprises culturing testis cells using a medium containing glial cell derived neurotrophic factor (GDNF) or an equivalent thereto to obtain pluripotent stem cells. The medium can further contain leukemia inhibitory factor (LIF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and the like. Using the production method of the present invention, it is possible to produce pluripotent stem cells, which have conventionally been only obtainable from fertilized eggs, embryos and the like, from a postnatal individual. Using the pluripotent stem cells, it is possible to construct diverse tissues having histocompatibility for autotransplantation, and the pluripotent stem cells are useful in medical fields such as regeneration medicine and gene therapy. Also, the pluripotent stem cells are useful in the field of biotechnology because they can be used to prepare transgenic animals, knockout animals and the like.