14 results about "Genetically modified mouse" patented technology

The invention discloses a construction method of a conditional knock-down dynactin animal model of astrocytes and an application of the animal model of the conditional knock-down dynactin animal model of the astrocytes. According to the method, a Dctn1LoxP gene knock-in mouse is hybridized with an Aldh1l1-Cre / ERT2 transgenic mouse, a target genotype mouse is obtained through three rounds of breeding, 100mg / kg Tamoxifen is continuously injected into the intraperitoneal cavity of the 2-month-old mouse for 5 days, and specific knock-down of dynactin in brain and spinal astrocytes is realized, including knockout of p150Glue and reduction of DCTN4, p50 and Arp1alpha protein levels. The model has the advantages of being high in specificity, permanent in intervention aging and capable of covering multiple life stages, the defects of a traditional model are overcome, the model can be used for researching the influence of dynactin on astrocyte neurobiological functions, a reliable tool is provided for screening related targets of nervous system diseases, and the model has important application value.

Disclosed in the present disclosure is genetically modified mice in which immunoglobulin loci are modified to insert gene segments of a human immunoglobulin variable region. The mice can be bred normally and produce human-mouse chimeric antibodies including a human variable region and a mouse constant region. The present disclosure also provides a method for preparing the genetically modified mice and use of the mice.

The present invention provides genetically modified animals (e.g., mice), humanized heavy chain antibodies, humanized nanobodies, and methods for producing and using them. [Solution] Provided are genetically modified non-human animals (e.g., genetically modified mice) that can be designed to produce heavy chain antibodies that can be used to generate single-domain antibodies or nanobodies. In one embodiment, a genetically modified mouse is provided comprising a germline modification comprising deletion of nucleic acid sequences comprising one or more heavy chain C region genes; the genetically modified mouse expresses an IgG heavy chain antibody and secretes an IgG heavy chain antibody in its serum.

The application discloses a construction method and application of an NLRP3 humanized mouse model, and belongs to the technical field of genetic engineering. The construction method of the NLRP3 humanized mouse model comprises the step of mutating the 708th amino acid of mouse Nlrp3-201 protein into a non-acidic amino acid; the Ensembl ID of the mouse Nlrp3-201 is ENSMUST00000079476.10. It is verified that the 708th amino acid of the mouse NLRP3 protein is mutated into a non-acidic amino acid (for example, alanine), the NLRP3 of the obtained mutant transgenic mouse is similar to human NLRP3, and cannot be cut by caspase-3, and humanization is realized. The mutant mouse model can better reflect the biological processes such as human inflammasome activation, cell pyroptosis and inflammatory reaction, and provides a more accurate animal model for understanding human diseases and drug screening.

Disclosed in the present disclosure is genetically modified mice in which immunoglobulin loci are modified to insert gene segments of a human immunoglobulin variable region. The mice can be bred normally and produce human-mouse chimeric antibodies including a human variable region and a mouse constant region. The present disclosure also provides a method for preparing the genetically modified mice and use of the mice.

This invention discloses a method for preparing Huangda tea polysaccharide L2-1 and its use in preventing and improving Alzheimer's disease. Huangda tea polysaccharide L2-1 has a total sugar content of 91.89%, a protein content of 1.19%, and a uronic acid content of 13.18%. The monosaccharide composition and its molar ratio are arabinose:rhamnose:mannose:glucose:galacturonic acid = 0.169:0.256:0.464:1:1.396. The Huangda tea polysaccharide L2-1 prepared by this invention can significantly improve the survival rate of L-Glu-induced PC12 cells and restore cell morphology, enhance the learning and memory abilities of APP / PS1 transgenic mice, inhibit the excessive activation of astrocytes in mouse brain tissue, and reduce neuroinflammation in the mouse brain. Huangda tea polysaccharide L2-1 has the function of improving / treating Alzheimer's disease.

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG / Il2rg KO / hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

Relapsing remitting multiple sclerosis (RRMS) is the most common form of multiple sclerosis, affecting more than 80% of MS patients. RRMS is comprised of two phases: the auto-inflammatory episodes, in which the immune system is actively destroying myelin, alternate with remission phases. Currently there is no cure for this devastating disease. The present disclosure provides compositions and methods useful for inducing remyelination. The methods are useful for promoting remyelination to treat diseases and disorders such as MS. The present disclosure describes compositions and methods useful for inhibiting LRP1 activity. In one aspect, a siRNA against LRP1 can be used. It is disclosed that myelination can be regulated by inhibiting the interaction of LRP1 and p75NTR and that it inhibits activation of Rho-A.

To provide a mouse that expresses a light chain containing the human λ variable region and the mouse constant region. [Solution] A genetically modified mouse expressing a human λ variable (hVλ) sequence is provided (including mice expressing the hVλ sequence from the endogenous mouse λ light chain locus, mice expressing the hVλ sequence from the endogenous mouse κ light chain locus, and mice expressing the hVλ sequence from a transgene or episome), wherein the hVλ sequence is linked to a mouse constant sequence. A mouse is provided that serves as the source of somatically mutated human λ variable sequences useful for the production of antigen-binding proteins. A composition and method for producing an antigen-binding protein containing a human λ variable sequence containing a human antibody is also provided.

Genetically modified mice and methods for making an using them are provided, wherein the mice comprise a replacement of all or substantially all immunoglobulin heavy chain V gene segments, D gene segments, and J gene segments with at least one light chain V gene segment and at least one light chain J gene segment. Mice that make binding proteins that comprise a light chain variable domain operably linked to a heavy chain constant region are provided. Binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Modified cells, embryos, and mice that encode sequences for making the binding proteins are provided.

This invention relates to the field of biotechnology and provides a gene-modified mouse model for tracking migratory organisms, its construction method, and its applications. The invention achieves precise labeling of endogenous migratory organisms by fusing the key structural protein TSPAN4 of the migratory organism with the fluorescent tag RFP and the modification tag Avi-tag, and site-specifically integrating it into the H11 site of mice, thus obtaining a TSPAN4-overexpressing transgenic mouse model. By introducing an LSL structure, the fusion gene is kept in a state of expression shutdown, achieving temporal and spatial specific activation only after mating with tissue-specific Cre tool mice. Multidimensional validation has shown that this model can accurately track migratory organisms in placental trophoblast cells, providing a standardized tool for assessing disease progression under physiological and pathological conditions through differences in migratory organism trajectory, inclusion packaging, and assembly, and can be directly applied to mechanistic studies and drug screening for diseases such as adverse pregnancy outcomes.

The invention discloses a composition containing cerebroprotein hydrolysate as well as a preparation method and application thereof. The composition has the main effects of improving memory, tranquilizing and allaying excitement and assisting digestion. Experiments prove that the combination of the deer brain protein hydrolysate, the pig brain protein hydrolysate and the bovine collagen peptide powder can improve the learning and memory ability of transgenic mice with Alzheimer's disease, and the combination of the deer brain protein hydrolysate, the pig brain protein hydrolysate and the bovine collagen peptide powder can further repair damaged nerve cells. The sea-buckthorn can reduce damage caused by oxygen free radicals and accelerate removal of free radicals in the body. Hawthorn and endothelium corneum gigeriae galli can improve the digestive function of a user, so that nutritional ingredients in the composition are fully absorbed by a human body. And the anti-oxidation effect of the vitamin C and the vitamin B5, the nervous system health maintaining effect of the vitamin B1, the vitamin B6 and the vitamin B12 and the carbohydrate fat protein hydrolysis accelerating effect of the vitamin B3 are supplemented, so that the whole formula composition has a certain effect of preventing the Alzheimer's disease and has a good application prospect.