A genetically modified rodent is provided that comprises a modified Acvr1 gene that comprises a conditional altered exon 7 encoding R258G in antisense orientation, flanked by site-specific recombinase recognition sites, wherein the altered exon is inverted to sense orientation upon action of a recombinase, resulting in ectopic bone formation.

Described herein is a method for producing a chimeric non-human animal expressing a human ETV2 gene comprising: a) generating an ETV2 null non-human animal cell, wherein both copies of the non-human ETV2 gene carry a mutation that prevents production of functional ETV2 protein in said non-human animal; b) creating an ETV2 null non-human blastocyst by somatic cell nuclear transfer comprising fusing a nucleus from said ETV2 null non-human animal cell of a) into an enucleated non-human oocyte and activating said oocyte to divide so as to form an ETV2 null non-human blastocyst; c) introducing human stem cells into the ETV2 null non-human blastocyst of b); and d) implanting said blastocyst from c) into a pseudopregnant surrogate non-human animal to generate a chimeric non-human animal expressing human ETV2.

The present invention includes compositions and methods for treating diseases or disorders associated with pathological calcification or pathological ossification. In certain embodiments, the diseases or disorders are selected from the group consisting of Generalized Arterial Calcification of Infancy (GACI), Idiopathic Infantile Arterial Calcification (IIAC), Ossification of the Posterior Longitudinal Ligament (OPLL), hypophosphatemic rickets, osteoarthritis, calcification of atherosclerotic plaques, PXE, hereditary and non-hereditary forms of osteoarthritis, ankylosing spondylitis, hardening of the arteries occurring with aging, calciphylaxis resulting from end stage renal disease and progeria.

The present application relates to a non-human mammal model of a human neurodegenerative disorder, methods of producing the non-human mammal model, and methods of using the non-human mammal model to identify agents suitable for treating a neurodegenerative disorder. The present application also relates to methods of treating neurodegenerative disorders and restoring normal brain interstitial potassium levels.

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.

Disclosed herein are rodents (such as, but not limited to, mice and rats) genetically modified to comprise a humanized Cxcl13 gene. The rodents disclosed herein have been shown to support better engraftment and proliferation of human cells such as chronic lymphocytic leukemic cells. Compositions and methods for making such genetically modified rodents, as well as methods of using such genetically modified rodents for testing candidate therapeutic agents (e.g., candidate anti-cancer drugs), are provided.

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.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized TRKB 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 TRKB locus express a human TRKB protein or a chimeric transthyretin protein, fragments of which are from human TRKB. Methods are provided for using such non-human animals comprising a humanized TRKB locus to assess in vivo efficacy of human-TRKB-targeting reagents such as nuclease agents designed to target human TRKB.

Methods for treating, and for identifying novel treatments for, neurodegenerative diseases, as well as animal and cellular models. The present disclosure shows that age dependent accumulation of genomic lesions leads to the production of RNA molecules within neurons that mimic viruses and intrinsically activate innate immune signaling, which triggers neurodegeneration. This hypothesis is supported by the results shown herein elucidating the mechanism of neurodegeneration in two mouse lines that specifically express different isoforms of the human amyloid precursor protein (hAPP) gene, which is associated with Alzheimer's disease (AD), exclusively in olfactory sensory neurons (OSNs) in the nose.

Methods and compositions are provided for making non-human animals with reduced tolerance of a foreign antigen of interest and making antigen-binding proteins against that foreign antigen of interest using such animals. The methods and compositions employ CRISPR/Cas9 systems using multiple guide RNAs to reduce or eliminate expression of a self-antigen homologous to or sharing an epitope of interest with the foreign antigen of interest or to reduce or eliminate expression of an epitope on the self-antigen that is shared with the foreign antigen of interest.