The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I and MHC II polypeptides and/or human or humanized β2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

The present invention relates to a Crumbs homologue (CRB) therapeutic for use as a medicament or in a method of treatment or prophylaxis, for example in the treatment or prophylaxis of a retinal disorder due to mutations in the Crumbs homologue-1 (CRB1) gene, such as Leber's congenital amaurosis 8 (LCA8) or retinitis pigmentosa 12 (RP12). In particular, the present invention relates to a recombinant viral vector comprising CRB2 or modified non-toxic forms of either CRB1 or CRB3 that resemble CRB2.

An object of the present invention is to provide a humanized mouse in which human hematopoietic stem cells can be engrafted for a long term. The present invention relates to a humanized rodent having human neutrophils circulating in a periphery, obtained by transplanting a human hematopoietic stem cell into a human G-CSF gene knock-in rodent, which is an immunodeficient rodent deficient in a G-CSF receptor function by knock-in of a human G-CSF gene at a G-CSF receptor locus, wherein a human G-CSF is expressed and a rodent G-CSF receptor is not expressed.

The present invention provides a method of treating myointimal proliferation by administering a recombinant human soluble ectonucleotide pyrophosphatase phosphodiesterase (hsNPP1), active fragment or fusion protein thereof.

The present invention provides: a novel nucleic acid construct encoding a functional fragment of a Trk family member; and use of the nucleic acid construct. A nucleic acid construct in accordance with an embodiment of the present invention encodes a fusion polypeptide including an intracellular domain of Trk and a membrane localization sequence.

The present disclosure provides an immunodeficient NOD.Cg-Prkdc.sup.scidIl2rg.sup.tm1Wjl/SzJ (NSG™) mouse models that comprise an inactivated mouse Flt3 allele, a nucleic acid encoding human interleukin 3 (IL3), a nucleic acid encoding human granulocyte/macrophage-stimulating factor (GM-CSF), a nucleic acid encoding human stem cell factor (SCF), and a HLA-A2/H2-D/B2M transgene encoding (i) a human B2-microglubulin (B2M) covalently linked to MHC class 1, alpha 1, and alpha2 binding domains of a human HLA-A2.1 gene and (ii) alpha3 cytoplasmic and transmembrane domains of murine H2-db.

The present disclosure belongs to the technical field of bioengineering, and relates to a method for constructing a Ptgds gene knockout rat model with spontaneous kidney yin deficiency. The method includes the following steps: 1) designing target sequences Ptgds-sgRNA1/2; 2) purifying Cas9mRNA and the Ptgds-sgRNA1/2; 3) conducting targeted knockout on a sequence fragment in the Ptgds gene using a CRISPR/Cas9 system; 4) injecting the purified Cas9mRNA, the purified Ptgds-sgRNA1/2, and a Ptgds knockout gene into rat embryos to obtain neonatal rats; 5) conducting genetic identification to select heterozygous rats; and 6) conducting breeding on the heterozygous rats with wild-type rats for multiple generations to obtain the Ptgds gene knockout rat model. In the present disclosure, the method has a high accuracy of gene modification, a targeting specificity, and a short experimental period.

A method of promoting axonal regeneration can include directing neuronal lipid synthesis away from triglyceride synthesis and toward phospholipid synthesis. The method can include administering to the patient a therapeutically effective amount of an inhibitor compound selected from the group consisting of a Lipin-1 inhibitor, a diglyceride acyltransferase inhibitor, and combinations thereof or administering a gene editing therapy to the patient that reduces expression of LIPIN1 or a diglyceride acyltransferase gene.

The present invention provides isolated IL-33 proteins, active fragments thereof and antibodies, antigen binding fragments thereof, against IL-33 proteins. Also provided are methods of modulating cytokine activity, e.g., for the purpose of treating immune and inflammatory disorders.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized coagulation factor XII (F12) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized F12 locus express a human coagulation factor XII protein or a chimeric coagulation factor XII protein, fragments of which are from human coagulation factor XII. Methods are provided for using such non-human animals comprising a humanized F12 locus to assess in vivo efficacy of human-coagulation-factor-XII-targeting reagents such as nuclease agents designed to target human F12. A short isoform of F12 that is produced locally in the brain, and methods of using the short isoform, are also provide.