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

Non-human animal cells and non-human animals comprising a humanized ACE2 locus and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized ACE2 locus express a human ACE2 protein or a chimeric ACE2 protein, fragments of which are from human ACE2. Methods are also provided for using such non-human animals comprising a humanized ACE2 locus to assess in vivo ACE2 activity, e.g., coronavirus infection and/or the treatment or prevention thereof.

Nucleic acid constructs and compositions that allow insertion and/or expression of a retinoschisin coding sequence are provided. Nuclease agents targeting RS1 loci are provided. Compositions and methods of using such constructs for integration into a target genomic locus and/or expression in a cell are also provided. Methods of treating X-linked juvenile retinoschisis using the nucleic acid constructs and compositions are also provided.

An object of the present invention is to provide an evaluation system capable of detecting an extracellular purinergic receptor ligand minimally invasively, chronologically and systemically, and the present invention provides a genetically modified non-human animal expressing a first fusion protein and a second fusion protein for detecting an extracellular purinergic receptor ligand, in which the first fusion protein comprises a membrane protein that binds to a purinergic receptor ligand, and a first reporter protein, and the second fusion protein comprises a protein that binds to the membrane protein bound to the ligand, and a second reporter protein; and a cell thereof.

Provided is an obsessive-compulsive disorder animal model and a production method thereof, in which a neuronal circuit connecting the basolateral amygdala (BLA) and the dorsomedial striatum (DMS) is activated. In the present disclosure, it was confirmed that the BLA and DMS are connected to each other, and that when the BLA-DMS neuronal circuit is activated, there is a large increase in checking, repeating, cleaning, and collecting, which are compulsive behaviors representative of obsessive-compulsive disorder, and a decrease in cognitive flexibility. Therefore, animals in which the BLA-DMS neuronal circuit is activated may be useful as animal models for studying obsessive-compulsive disorder. In particular, the obsessive-compulsive disorder animal model can reproduce all of the compulsive behaviors and thus may become the first animal model to provide an understanding of the interactions between anxiety behaviors and compulsive behaviors, which existing animal models have not been able to provide.

The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) LAG3, and methods of use thereof.

Non-human animals comprising a human or humanized IL-4 and/or IL-4Rα nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous IL-4 gene and/or IL-4Rα gene with a human IL-4 gene and/or IL-4Rα gene in whole or in part, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized IL-4 gene under control of non-human IL-4 regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4-encoding sequence with human IL-4-encoding sequence at an endogenous non-human IL-4 locus. Non-human animals comprising a human or humanized IL-4Rα gene under control of non-human IL-4Rα regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4Rα-encoding sequence with human or humanized IL-4Rα-encoding sequence at an endogenous non-human C IL-4Rα locus. Non-human animals comprising human or humanized IL-4 gene and/or IL-4Rα sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

The present disclosure relates to genetically modified non-human animals that express a fusion protein including B2M and FcRn, and methods of use thereof. In some embodiments, the animals can have a B-NDG background. In some embodiments, the endogenous B2M gene is knocked out in the animals.

Mice, embryos, cells, and tissues having a restricted immunoglobulin heavy chain locus and an ectopic sequence encoding one or more ADAM6 proteins are provided. In various embodiments, mice are described that have humanized endogenous immunoglobulin heavy chain loci and are capable of expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof that is functional in a male mouse. Mice, embryos, cells, and tissues having an immunoglobulin heavy chain locus characterized by a single human V.sub.H gene segment, a plurality of human D.sub.H gene segments and a plurality of human J.sub.H gene segments and capable expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof are also provided.