This disclosure relates to genetically modified rodent animals and rodent models of human diseases. More specifically, this disclosure relates to genetically modified rodents whose genome comprises a humanized Il1rl2 gene (coding for the IL1rl2 subunit of the IL-36R protein) and human IL-36α, β and γ ligand genes. The genetically modified rodents disclosed herein display enhanced skin and intestinal inflammation as a preclinical model of psoriasis and IBD, respectively, and serve as a rodent model of human DITRA disease.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD94 and/or NKG2A, and methods of use thereof.

Transgenic non-human animals, e.g., rodents, e.g., mice comprising genomic mutations that inactive all of the serpinlA genes and thus lack any functional serpinA1 genes. As a result of the genomic mutations, the animals express no hepatic or circulatory AAT protein. Also provided herein are cells and tissues derived from the transgenic mice.

Mice comprising a modified p21-activated kinase (Pak) inhibitor domain (PID*), optionally linked with GST and capable of constitutive expression of PID are provided. Also provided are cells, tissue, and organs obtainable from such mice, and methods for producing mice comprising a modified p21-activated kinase (Pak) inhibitor domain (PID*).

Methods for treating amyotrophic lateral sclerosis (ALS). The methods include administering to a subject in need thereof a therapeutically effective amount of at least one small conductance calcium-activated potassium (SK) channel activator or a pharmaceutically acceptable salt or solvate thereof. Pharmaceutical compositions for the treatment of ALS, including a therapeutically effective amount of at least one SK channel activator, or a pharmaceutically acceptable salt or solvate thereof, and at least one excipient, adjuvant, or pharmaceutically acceptable carrier.

Disclosed herein are nucleic acids encoding for and proteins expressing chimeric C1q polypeptides, non-human animals comprising said nucleic acids, and methods of making or using said non-human animals.

Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized a proliferation-inducing ligand gene. Non-human animals and cells that express a human or humanized a proliferation-inducing ligand protein from an endogenous a proliferation-inducing ligand locus are described.

The inventive technology is directed to the generation of a novel transgenic mammalian model for the study of Laing distal myopathy. The novel animal model of the invention may include a transgenic animal, and preferably a transgenic mouse, expressing the β-myosin R1500P mutation transgene that produces one or more phenotypes associated with MPD1. The β-myosin R1500P mutation transgene may further be selectively expressed in fast muscle tissue of the transgenic animal.

Provided is a method for preparing a PD-1 gene-modified humanized animal model. The method utilizes the CRIPSR/Cas9 technique to replace partial fragments of a mouse PD-1 gene with fragments of a human PD-1 gene using homologous recombination by constructing a targeting vector, thereby preparing a gene-modified humanized mouse. This mouse can normally express a PD-1 protein containing the functional domain of the human PD-1 protein, and can be used as an animal model for mechanism research regarding PD-1, PD-L1 and other signals, for screening regulators, and for toxicological research. The method has an important and high application value in studies on functions of the PD-1 gene and in the development of new drugs.

The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain comprising an alpha chain variable domain and a beta chain comprising a beta chain variable domain and the library comprises more than one TRAV gene product and/or more than one TRBV gene product, wherein the beta chain variable domain does not comprise one or more of a TRBV5-1, 5-3, 5-4, 5-5, 5-6, 5-7 or 5-8 gene product and wherein the plurality of TCRs do not consist essentially of TCRs comprising a TRAV12-2 gene product from a natural repertoire and a TRBV6 gene product from a natural repertoire and TCRs comprising a TRAV21 gene product from a natural repertoire and a TRBV6 gene product from a natural repertoire.