212 results about "Genetically modified mouse" patented technology

In humans, approximately 60% of expressed immunoglobulin light chains are of the Kappa type and 40% of the Lambda type. In mice, there is almost no expression from the Lambda locus and over 95% of light chains are of Kappa type. The present invention discloses, among other things, transgenic mice carrying most of the human Ig Lambda light chain locus in their genome. The resulting mice express light chains with Kappa / Lambda ratio similar to the human ratio. Breeding of HuIg Lamda mice to Kappa-deficient mice also is described, as well as the generation of human monoclonal antibodies from transgenic mice with human Ig Lambda locus.

A transgenic non-human animal, such as a mouse, has a genome that include a nucleic acid construct having at least one transcriptional regulatory sequence capable of directing expression in B cells of the animal, wherein the transcriptional regulatory sequence is operably linked to a nucleic acid encoding a miR155 gene product. A method of testing the therapeutic efficacy of an agent in treating or preventing a lymphoproliferative condition includes assessing the effect(s) of the agent on a transgenic non-human animal.

The invention discloses a preparation method of a staphylococcus aureus CRISPR / Cas9 system and an application of the system in constructing a genetically modified mouse model. The staphylococcus aureus CRISPR / Cas9 system is composed of two components, namely Cas9 mRNA and gRNA, wherein a preparation method of the Cas9 mRNA is achieved by adding a T7 promoter to the upstream region of original Cas9 coding DNA, and a preparation method of the gRNA is achieved by adding the T7 promoter to the upstream region of an original gRNA coding sequence. The staphylococcus aureus Cas9 mRNA and gRNA, which are injected to mouse fertilized embryos through micro-injection, can achieve gene editing and modification of various types, such as single-gene knockout, multi-gene knockout and / or gene knock-in and the like, on the mouse fertilized embryos; therefore, the CRISPR / Cas9 system has a good application prospect in the aspects of fertilized embryo gene editing and modification of such animals as mouse and the like as well as construction of animal models.

The invention provides nonhuman transgenic animals with a disrupted FHIT gene. The invention further provides transgenic mice in which one or both Fhit alleles have been inactivated. Preferably, the Fhit-deficient mice develop multiple tumors of both visceral and sebaceous origin, similar to those of Muir-Torre familial cancer syndrome. The present invention further relates to the generation of these transgenic mice and their use as model systems to study the effects of carcinogenic agents in promoting clonal expansion of neoplastic cells in cancers, preferably gastrointestinal cancers of which Muir-Torre syndrome is a subset. The invention further relates to testing therapeutic agents for their efficacy in the prevention and treatment of cancer, preferably gastrointestinal cancer.

The invention provides nonhuman transgenic animals with a disrupted FHIT gene. The invention further provides transgenic mice in which one or both Fhit alleles have been inactivated. Preferably, the Fhit-deficient mice develop multiple tumors of both visceral and sebaceous origin, similar to those of Muir-Torre familial cancer syndrome. The present invention further relates to the generation of these transgenic mice and their use as model systems to study the effects of carcinogenic agents in promoting clonal expansion of neoplastic cells in cancers, preferably gastrointestinal cancers of which Muir-Torre syndrome is a subset. The invention further relates to testing therapeutic agents for their efficacy in the prevention and treatment of cancer, preferably gastrointestinal cancer.

Immunization of human antibody-producing transgenic mice, which have been created using genetic engineering techniques, with AILIM molecule as an antigen resulted in various human monoclonal antibodies capable of binding to AILIM and capable of controlling a variety of biological reactions (for example, cell proliferation, cytokine production, immune cytolysis, cell death, induction of ADCC, etc.) associated with AILIM-mediated costimulatory signal (secondary signal) transduction. Furthermore, it has been revealed that the human monoclonal antibody is effective to treat and prevent various diseases associated with AILIM-mediated costimulatory signal transduction, being capable of inhibiting the onset and / or advancement of the diseases.

Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a humanization of an extracellular loop of an endogenous NaV channel gene, in particular a humanization of the one or more extracellular pore loops of a NaV1.7 channel protein. Genetically modified non-human animals are also provided, wherein the genetic modification comprises replacement of an endogenous NaV channel gene, in particular a replacement of the endogenous NaV1.7 gene with a human NaV1.7 gene, and wherein the genetically modified non-human animals are capable of generating action potentials and communicating through the excitable cells of the genetically modified non-human animals via the expressed human or humanized NaV1.7 protein the surface of the excitable cells. Genetically modified mice are described, including mice that express the human or humanized NaV1.7 gene from the endogenous NaV1.7 locus, and wherein the mice comprise functional β-subunits.

The invention provides compositions and methods for the generation of novel non-human transgenic animals which contain an alteration in a gene of interest. These transgenic animals are capable of generating antibodies, e.g., human monoclonal antibodies, specific for the product of a gene of interest that has been functionally disrupted in the transgenic animal. Furthermore, the methods and compositions of the invention are suitable for use in the treatment, diagnosis, and imaging of disease.

The invention provides for transgenic mice whose genomes comprise a gene encoding human cyclooxygenase-2 under the control of a neuron-specific promoter. The transgenic mice of the instant invention express human cyclooxygenase-2 mRNA in neuronal cells of their hippocampi at increased levels relative to the level of human cyclooxygenase-2 mRNA expressed in their cerebral white matter. Moreover, neuronal cell cultures derived from the transgenic mice of the instant invention arc more susceptible to aggregated Abeta25-35 peptide-mediated impairment of redox activity relative to those derived from mice non-transgenic for the human cyclooxygenase-2 gene. These transgenic animals and the neuronal cultures derived therefrom are useful iii elucidating the pathophysiological bases of neurodegenerative diseases and in improving the diagnosis and treatment of these disorders.

The invention relates to a humanized gene genetically modified non-human animal, particularly a genetically modified rodent, especially a genetically modified mouse, and in particular relates to a construction method of a humanized TIGIT gene animal model and application of the model in the biomedicine field.

Genetically modified non-human animals and methods and compositions for making and using the same are provided, wherein the genetic modification comprises a humanization of an endogenous signal-regulatory protein gene, in particular a humanization of a SIRPα gene. Genetically modified mice are described, including mice that express a human or humanized SIRPα protein from an endogenous SIRPα locus.

The present invention relates to transgenic mice and isolated transgenic mouse cells, the mice and mouse cells comprising a disrupted H2 class I gene, a disrupted H2 class II gene, a functional HLA class I transgene, and a functional HLA class II transgene. In embodiments, the transgenic mouse or mouse cells are deficient for both H2 class I and class II molecules, wherein the transgenic mouse comprises a functional HLA class I transgene and a functional HLA class II transgene. In embodiments, the transgenic mouse or mouse cell has the genotype HLA-A2+HLA-DR1+β2m°IAβ°. The invention also relates to methods of using a transgenic mouse of the invention.

This invention is related to adenoviral (Ad) vectors and their applications in the field of genetic medicine, including gene transfer, gene therapy, and gene vaccination. More specifically, this invention is related to the Ad vectors that carry the minimal cis-element of the Ad genome (mini-Ad vector) and are capable of delivering transgenes and / or heterologous DNA up to 36 kb. The generation and propagation of the mini-Ad vectors require trans-complementation of a packaging-attenuated and replication-defective helper Ad (helper) in an Ad helper cell line. This invention further comprises a methodology for generating a mini-adenoviral (mini-Ad) vector for use in gene therapy of hemophilia and animal test systems for in vivo evaluation of the Ad vectors. More specifically, this invention describes factor VIII (FVIII) Ad vectors that only contain minimal cis-elements of the Ad genome (so called mini-Ad) and comprise a human FVIII cDNA with other supporting DNA elements up to 36 kb. The FVIII mini-Ad can be generated and preferentially amplified through the assistance of a packaging-attenuated helper Ad and a helper cell line. This invention also reports designs and methods for producing transgenic mouse models that can be used for in vivo testing the mini-Ad.

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.