81 results about "Deficient mouse" patented technology

Disclosed herein among other MN/CA IX-related inventions are new MN/CA IX-specific antibodies generated from MN/CA IX-deficient mice, preferably monoclonal antibodies and immunoreactive fragments and engineered variants thereof. Subsets of the new antibodies are to either the proteoglycan-like (PG) domain or to the carbonic anhydrase (CA) domain of MN/CA IX, and methods are provided by which antibodies can be prepared to the other MN/CA IX domains. Such new MN/CA IX-specific antibodies, fragments and variants are useful diagnostically/prognostically and therapeutically for cancer and precancer. Particularly preferred are the new monoclonal antibodies, fragments and variants that are specific for the non-immunodominant epitopes of MN/CA IX, which antibodies are, among other uses, useful to detect soluble MN/CA IX (s-CA IX) in body fluids, alone but preferably in combination with antibodies specific to the immunodominant epitopes of MN/CA IX, for example, in a sandwich assay.

Disclosed herein is the discovery of a soluble MN/CA IX (s-CA IX) in body fluids, such as, urine and serum. Said s-CA IX comprises the extracellular domain of CA IX or portions thereof. The predominant s-CA IX species is the extracellular domain comprising a proteoglycan-like (PG) domain and carbonic anhydrase (CA) domain, and having a molecular weight of about 50/54 kilodaltons (kd) upon Western blot. A smaller s-CA IX form of about 20 to about 30 kd comprising the CA domain or parts thereof, not linked to the PG domain, has also been found in body fluids. Diagnostic/prognostic methods for precancer and cancer that detect or detect and quantitate said s-CA IX in body fluids, are described. Also disclosed herein is the coexpression of CA IX and HER-2/neu/c-erbB-2 that provides parallel, alternative and potentially synergistic diagnostic/prognostic and therapeutic strategies for precancer and cancer. Further disclosed are new MN/CA IX-specific antibodies generated from MN/CA IX-deficient mice, preferably monoclonal antibodies and immunoreactive fragments and engineered variants thereof. Such new MN/CA IX-specific antibodies, fragments and variants are useful diagnostically/prognostically and therapeutically for cancer and precancer. Particularly preferred are the new monoclonal antibodies, fragments and variants that are specific for the non-immunodominant epitopes of MN/CA IX, which antibodies are, among other uses, useful to detect soluble MN/CA IX (s-CA IX) in body fluids, alone but preferably in combination with antibodies specific to the immunodominant epitopes of MN/CA IX, for example, in a sandwich assay.

The present invention relates to the production of adenosine deaminase (ADA) deficient mice and the use of such mice as an animal model for dysfunctions associated with elevated adenosine levels. Also, provided by the present invention are methods of treating dysfunctions associated with elevated adenosine levels and methods of screening compounds for pharmaceutical activity in the treatment of dysfunctions associated with elevated adenosine levels.

The invention discloses a method for establishing an immunodeficiency mouse model. The method comprises the following steps of: (1) constructing DNA (deoxyribonucleic acid) which enables functions of an immune related gene in a mouse cell to be lost; (2) purifying mRNA (messenger ribonucleic acid), and cryopreserving in a super-purified water of RNAase free; (4) feeding a pregnant female mouse and a pseudopregnant female mouse under an SPF (specific pathogen free) level feeding condition; (5) taking a fallopian tube from the abdominal cavity of the pregnant female mouse in the step (4), and collecting fertilized ovum; (6) injecting the mRNA obtained in the step (3) into the pronucleus of the fertilized ovum in the step (5) by using a microinjection method; (7) transplanting the fertilized ovum obtained in the step (6) into the body of the pseudopregnant female mouse obtained in the step (4), and enabling the pseudopregnant female mouse to culture the second generation; (8) establishing a stable deficient mouse strain. The method has the advantages that a mouse model which completely does not have immunological rejection to allotransplantation can be obtained for testing.

A PGD(2) receptor (DP) deficiency enhances tumor progression accompanied by abnormal vascular expansion. In tumors, angiogenic endothelial cells highly express DP receptor, and its deficiency accelerates vascular leakage and angiogenesis. Administration of a synthetic DP agonist, BW245C, markedly suppresses tumor growth as well as tumor hyperpermeability in WT mice, but not in DP-deficient mice. In a corneal angiogenesis assay and a modified Miles assay, host DP deficiency potentiates angiogenesis and vascular hyperpermeability under COX-2-active situation, whereas exogenous administration of BW245C strongly inhibits both angiogenic properties in WT mice. In an in vitro assay, BW245C does not affect endothelial migration and tube formation, processes that are necessary for angiogenesis; however, it strongly improves endothelial barrier function via an increase in intracellular cAMP production. PGD(2)/DP receptor is a newly identified regulator of tumor vascular permeability, indicating DP agonism can be exploited as a therapy for the treatment of cancer.

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.

This invention demonstrates that FC function via TNF-α to affect function of HSC. FC from TNF-α deficient mice are impaired in facilitating HSC engraftment in both the syngeneic and allogeneic models. Co-incubation of FC with HSC results in significant increase in TNF-α at the mRNA and protein level, and increase in transcript for Bcl-3 in HSC. Furthermore, neutralization of TNF-α results in the loss of FC ability to increase HSC clonogenicity and survival, as well as to upregulate Bcl-2 transcript in HSC, demonstrating a critical role for TNF-α in FC function. These results offer a mechanism of action for HSC regulation by accessory cells in the bone marrow and confirm the advantage of their co-transplantation with HSC to improve graft efficiency.

The invention relates to a three-dimensional culture system based on thermo-sensitive biogel. The three-dimensional culture system is prepared by combining the following reagents: thermo-sensitive biogel, digestive fluid required for separating and culturing tumor cells, a basal culture medium and a human intestinal stem cell culture medium. The invention also provides a method for establishing acolorectal cancer patient-derived xenograft model through the three-dimensional culture system based on thermo-sensitive biogel. The three-dimensional culture system has the advantages that colorectalcancer cells can be further amplified and grown in the three-dimensional culture system based on thermo-sensitive biogel, and the tumor formation capability of the colorectal cancer cells in the immune deficient mice can be enhanced. Polyclonal tumor cells cultured in the system have high subcutaneous tumor formation capability in nude mice. The three-dimensional culture system has the advantagesof simple preparation method and mature technology, and is capable of greatly reducing the time and the cost for establishing the human-derived colorectal cancer xenograft model.

The mdx mouse is a model of Duchenne muscular dystrophy. The present invention describes that mdx mice exhibited clinically relevant cardiac phenotypes. A non-invasive method of recording electrocardiograms (ECGs) was used to a study mdx mice (n=15) and control mice (n=15). The mdx mice had significant tachycardia, consistent with observations in patients with muscular dystrophy. Heart-rate was nearly 15% faster in mdx mice than control mice (P<0.01). ECGs revealed significant shortening of the rate-corrected QT interval duration (QTc) in mdx mice compared to control mice (P<0.05). PR interval duration were shorter at baseline in mdx compared to control mice (P<0.05). The muscarinic antagonist atropine significantly increased heart-rate and decreased PR interval duration in C57 mice. Paradoxically, atropine significantly decreased heart-rate and increased PR interval duration in all mdx mice. Pharmacological autonomic blockade and baroreflex sensitivity testing demonstrated an imbalance in autonomic nervous system modulation of heart-rate, with decreased parasympathetic activity and increased sympathetic activity in mdx mice. These electrocardiographic findings in dystrophin-deficient mice provide new bases for diagnosing, understanding, and treating patients with Duchenne muscular dystrophy.

The present invention relates to an application of bone morphogenetic protein 4 in cancer inhibition. Specifically bone morphogenetic protein (BMP) has a liver cancer stem cell differentiation induction effect, wherein CD133 protein expression of liver cancer cell lines can be down-regulated and liver cancer cell line CD133+ liver cancer stem cell differentiation can be promoted with BMP4, and BMP4 can further be provided for inhibiting in vitro proliferation and self-renewal of liver cancer cell lines and inhibiting tumorigenicity of immune-deficient mice. The present invention further provides BMP4-induced liver cancer stem cell differentiation action mechanism.

The instant invention relates to a transgenic, non-human animal that carries a mutation in the gene encoding C-reactive protein (CRP). Preferably, the invention relates to an animal comprising a homozygous CRP-deficient mouse and techniques for producing such animals. The invention also relates to organs, tissues, cells, cell lines and sub-cellular fractions derived from such animals. Techniques for generating total or tissue-specific CRP knockout animals are also described. The invention further relates to the use of such knockout animals for the study of the role of CRP proteins in vivo or ex vivo, particularly in relation to its role in inflammatory pathway and in the etiology human diseases.

The invention relates to a method for in-vitro screening inducers, particularly to a method for in-vitro screening of PXR (pregnane X receptor) activation characteristics, which comprises the following steps: constructing a reporter gene vector; culturing cells, and screening G418 working concentration; carrying out transient transfection of cells; screening stably transfected cell clones; inducing and identifying stably transfected cell strain with a tested drug (ligand drug); and screening the PXR activation characteristics. When the PXR is activated by the ligand drug, the PXR can regulate the expression CYP3A gene. PXR gene-deficient mice lose drug inductivity of CYP3A. Contrarily, hPXR (human pregnane X receptor) receptor in activation state expressed in liver of a transgenic mouse can lead to continuous high expression of CYP3A enzyme. The method of the invention establishes critical technology for high-throughput screening based on the passway and carries out screening of PXR activation characteristics from mass compounds in a compound library at the early stage of drug development, and can reduce the risk of adverse drug interactions after the new drug comes into the market, and greatly reduce development cost.

The invention relates to a genetically-modified non-human animal and application thereof, in particular to a transgenic mouse model and application thereof in the aspect of screening of a targeted medicine. According to the transgenic mouse model and application thereof in the aspect of screening of the targeted medicine, by targetedly knocking out and replacing a mouse protein C gene by means ofa human protein C gene expression cassette, a humanized protein C knock-in mouse is generated. The mouse has fertility, and can hybridize with another mouse disease model (such as a mouse in the deficiency of a blood coagulation factor VIII or a blood coagulation factor IX) to produce a humanized protein C mouse disease model (such as a humanized protein C factor VIII-deficient mouse model or a humanized protein C factor IX-deficient mouse model). The mouse model can be used for studying functions in vivo of human protein C and human activated protein C (APC). The mouse model is the first mouse model used for testing a therapeutic candidate medicine, which targets the human protein C or the APC, in vivo, and has very high economic value and scientific research value.

The invention relates to the technical field of biology and in particular relates to a method for constructing a hepatitis B virus (HBV) infected mouse model and application of the HBV infected mouse model. The invention provides a method for constructing a high-ALT (alanine transaminase) HBV infected mouse model. The method for constructing the HBV infected mouse model comprises the step of medicating HBV genome DNA plasmid to a Tlr2 gene-deficient mouse, so that the HBV infected mouse model is constructed. The mouse model provided by the invention is relatively simple to construct, relatively easy in technological means and low in construction cost; besides, the adopted HBV plasmid vector is non-toxic, can not induce immune response of the mouse and also can avoid serious immunodeficiency in a chimera mouse model, and the obtained HBV infected model has higher blood serum ALT level and obvious liver inflammation expression.

The invention belongs to the technical field of body immunity, and discloses a detection model for a mouse intestinal mucosa epithelial barrier function and an intestinal mucosa immune tolerance cell. The model is characterized in that one part of Gal-1 deficient mice is subjected to Gal-1 intraperitoneal injection, and each mouse is injected with 0.25mg each time per day, and injection is carried out for 7 days; small intestines are respectively taken from the Gal-1 deficient mice, B6 mice and mice injected with Gal-1. The method comprises the following steps: obtaining the Gal-1 deficient mice, wherein the Gal-1 deficient mice are subjected to the Gal-1 intraperitoneal injection; respectively taking the intestines from the Gal-1 deficient mice, the B6 mice and the mice injected with Gal-1, and installing in a Ussing chamber system; measuring an epithelial barrier function; taking the small intestines to separate LPMC (Lamina Propria Mononuclear Cells), and detecting immune tolerance cells. The Gal-1 has an immunoregulation function, the intestinal mucosa is an important organ for forming oral tolerance, and the IEC (Intestinal Epithelial cCells) has an immune tolerance function.

The disclosure describes a unique animal model which is useful for studying the role of FGF14 in the central nervous system (CNS) and testing of potential drugs for treatment of CNS diseases. To provide this animal model, the Fgf14 gene is disrupted in mice by replacing the second and third exons with beta-galactosidase. Neuropharmacological studies are disclosed which show that the Fgf14 deficient mice have disrupted striatal-nigra and striatal-pallidal pathways resulting in increased excitatory input to the cortex. The paroxysmal hyperkinetic disorder in Fgf14 deficient mice phenocopies a form of dystonia, a disease often associated with dysfunction of the putamen.

Inoculation of ATM-deficient mice with probiotic microorganisms, such as L. johnsonii, changed immune parameters, decreased a marker of DNA damage and increased the lifespan of the mice. Compositions and methods described herein are useful for the treatment and prevention of Ataxia telangiectasia and other cancer-prone disease, such as p53 deficiency-associated cancers. Compositions and methods of the present invention are also useful for treating and preventing radiation-induced toxicity to normal tissue in a subject being exposed to radiation. Compositions and methods of the invention can increase lifespans in a simple, non-invasive manner.