The invention discloses a method for screening a therapeutic target of acute radiation-induced gastrointestinal syndrome and use of TIGAR target in the preparation of a medicine for treating radiation-induced gastrointestinal syndrome. The CreERT-loxP transgenic mouse model is used, in which quiescent intestinal crypt stem cells are effectively promoted to proliferate after exposure to high-dose ionizing radiation, to screen a therapeutic target that still has a therapeutic effect for radiation-induced gastrointestinal syndrome 18-24 h after ionizing radiation. Gene splicing occurs in particular cells in the CreERT-loxP transgenic mice only after the injection of tamoxifen, thereby regulating gene expression. The actual situation of initial exposure and then treatment after a nuclear accident is well simulated, so the invention is of great practical significance. The screened therapeutic target is developed into a medicine for treatment after nuclear accidents, to save precious time for the treatment after nuclear accidents.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD38, and methods of use thereof.

This document relates to methods and materials involved in the deconvolution of serum. For example, transgenic non-human animals (e g , transgenic mice) that secrete tagged (e.g., biotinylated) molecules from a particular tissue are provided.

The present disclosure relates to nucleic acid promoter sequences that are able to specifically express genes operatively linked to the promoter in brainstem and spinal motor neuron cells, and to methods for using such promoters to selectively express genes in motor neurons in vitro and in vivo. It is based, at least in part, on the discovery that the nucleic acid of SEQ ID NO: 1 functioned as a motor neuron-specific promoter and was successful in expressing transgenes in motor neuron cells in vivo. The present disclosure also relates to compositions that can increase the activity or expression level of miR-218 and to compositions that can decrease the expression of miR-218 target nucleic acids.

Provided herein are engineered TSC2 polypeptides, and nucleic acid sequences encoding them, in which the ability of a serine residue to be phosphorylated is altered. In some aspects, the TSC2 serine residue cannot be phosphorylated (e.g., by substituting the serine residue with an alanine residue). In some aspects, the TSC2 serine acts as if it is constitutively phosphorylated (e.g., by substituting the serine residue with a glutamic acid residue). Also provided herein are engineered immune cells comprising altered TSC2 polypeptides or nucleic acid sequences encoding them, and methods of making and using such engineered immune cells.

Described herein are methods of enhancing chromosomal homologous recombination to stimulate a loss of heterozygosity at a gene locus of interest in a living cell. These methods are driven by an enhancer component and a target-specific endonuclease component and proceed through a mechanism whereby: exogenous donor DNA that is homologous to the gene locus of interest is not introduced into the living cell; the desired allele of the gene locus of interest remains uncleaved; and the undesired allele is either uncleaved, cleaved at a single location, or cleaved at multiple locations. These methods have numerous applications, including the repair of risk alleles for disease prevention, the correction of heterozygous mutations in dividing cells, the design of cancer therapeutics, and the design of novel gene-drive strategies.

The invention relates to nucleic acid constructs for expression in mice for the reproduction of heavy chain only antibodies and V.sub.H domains, transgenic mice, related methods and uses.

The current Alzheimer's disease model mouse, developed by manipulating the expression of a gene directly related to distinctive pathology that is specific to the disease, such as acceleration of amyloid plaque deposition, is a model of a preclinical state, or of a pathology that is fundamentally different from human Alzheimer's disease. In view of the current state described above, the present invention addresses the problem of developing a non-human transgenic animal in which Alzheimer's pathology is more accurately reflected, and thereby elucidating a disease mechanism or contributing to drug discovery. In the present invention, by heterozygous knockout of the drebrin gene of a non-human Alzheimer's disease model animal used as a base, senescence risk can be imparted to the conventional non-human Alzheimer's disease model animal. Alzheimer's pathology is more accurately reflected in this non-human Alzheimer's disease model animal.

The present invention belongs to the technical field of protein and genetic engineering, and specifically discloses use of an erythropoietin human hepatocyte receptor B4 as a target in screening and preparing a biological formulation or medicament for increasing sensitivity to insulin. Also disclosed is use of an erythropoietin human hepatocyte receptor B4 in preparing an insulin-sensitized mouse model. On the basis of insulin signal regulation, a protein EphB4 capable of interacting with an insulin receptor (InsR) is found. The protein can interact with InsR, and insulin stimulation can promote the interaction between the two, which provides a basis for insulin resistance in the case of hyperinsulinaemia. Over-expression of EphB4 can promote degradation of InsR. Inhibition of EphB4 can enhance the sensitivity to insulin and improve insulin resistance.

The invention relates to synthetic polynucleotides encoding fukutin related protein (FKRP). The invention further relates to nucleic acid constructs comprising the synthetic polynucleotides and methods of using these synthetic polynucleotides to treat dystroglycanopathy disorders.