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

Abstract: Non-human animal cells and non-human animals comprising a humanized Cacng1 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 Cacng1 locus express a human CACNG1 protein or fragments thereof.

Abstract: Non-human animals suitable for use as animal models for Retinoschisis are provided. In some embodiments, provided non-human animals are characterized by a disruption in a Retinoschisin-1 locus. In some embodiments, provided non-human animals are characterized by a mutant Retinoschisin-1 gene. The non-human animals may be described, in some embodiments, as having a phenotype that includes the development of one or more symptoms or phenotypes associated with Retinoschisis. Methods of identifying therapeutic candidates that may be used to prevent, delay or treat Retinoschisis or eye-related diseases, disorders or conditions are also provided.

Abstract: 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.

Abstract: This disclosure relates to an animal model of human disease. More specifically, this disclosure relates to a rodent model of mood disorders such as unipolar depression and an anxiety disorder. Disclosed herein are genetically modified rodent animals that carry a humanized G protein-coupled receptor 156 (GPR156) gene that encodes a mutant human GPR156 protein comprising Asp at an amino acid position corresponding to position 533 in a full length wild type human GPR156 protein.

Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized KLKB1 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 KLKB1 locus express a human plasma kallikrein protein or a chimeric plasma kallikrein protein, fragments of which are from human plasma kallikrein. Methods are provided for using such non-human animals comprising a humanized KLKB1 locus to assess in vivo efficacy of human-KLKB 1-targeting reagents such as nuclease agents designed to target human KLKB1.

Abstract: Methods for introducing a scarless targeted genetic modification into a preexisting targeting vector are provided. The methods can use combinations of bacterial homologous recombination (BHR) and in vitro assembly to introduce such targeted genetic modifications into a preexisting targeting vector in a scarless manner.

Abstract: This disclosure relates to an animal model of human disease. More specifically, this disclosure relates to a rodent model of mood disorders such as unipolar depression and an anxiety disorder. Disclosed herein are genetically modified rodent animals that carry a humanized G protein-coupled receptor 156 (GPR156) gene that encodes a mutant human GPR156 protein comprising Asp at an amino acid position corresponding to position 533 in a full length wild type human GPR156 protein.

Abstract: Disclosed herein are rodents (such as, but not limited to, mice and rats) genetically modified to comprise a humanized Tslp gene, a humanized Tslpr gene, a humanized 117ra gene, or a combination thereof. Compositions and methods for making such genetically modified rodents, as well as methods of using such genetically modified rodents as an animal model for diseases such as allergic diseases and cancer are provided.

Abstract: Non-human animals suitable for use as animal models for Retinoschisis are provided. In some embodiments, provided non-human animals are characterized by a disruption in a Retinoschisin-1 locus. In some embodiments, provided non-human animals are characterized by a mutant Retinoschisin-1 gene. The non-human animals may be described, in some embodiments, as having a phenotype that includes the development of one or more symptoms or phenotypes associated with Retinoschisis. Methods of identifying therapeutic candidates that may be used to prevent, delay or treat Retinoschisis or eye-related diseases, disorders or conditions are also provided.

Abstract: Methods for introducing a scarless targeted genetic modification into a preexisting targeting vector are provided. The methods can use combinations of bacterial homologous recombination (BHR) and in vitro assembly to introduce such targeted genetic modifications into a preexisting targeting vector in a scarless manner.

Abstract: Methods and compositions are provided for assessing CRISPR/Cas-mediated non-homologous end joining (NHEJ) activity and/or CRISPR/Cas-induced recombination of a target genomic locus with an exogenous donor nucleic acid in vivo or ex vivo. The methods and compositions employ non-human animals comprising a CRISPR reporter such as a genomically integrated CRISPR reporter for detecting and measuring targeted excision of a sequence between two CRISPR/Cas nuclease cleavage sites or disruption of a sequence near a CRISPR/Cas nuclease cleavage site and/or measuring CRISPR/Cas-induced recombination of the CRISPR reporter with an exogenous donor nucleic acid to convert the coding sequence for a first reporter protein to the coding sequence for a different second reporter protein. Methods and compositions are also provided for making and using these non-human animals.

Abstract: Methods for introducing a scarless targeted genetic modification into a preexisting targeting vector are provided. The methods can use combinations of bacterial homologous recombination (BHR) and in vitro assembly to introduce such targeted genetic modifications into a preexisting targeting vector in a scarless manner.

Abstract: Non-human animals suitable for use as animal models for Retinoschisis are provided. In some embodiments, provided non-human animals are characterized by a disruption in a Retinoschisin-1 locus. In some embodiments, provided non-human animals are characterized by a mutant Retinoschisin-1 gene. The non-human animals may be described, in some embodiments, as having a phenotype that includes the development of one or more symptoms or phenotypes associated with Retinoschisis. Methods of identifying therapeutic candidates that may be used to prevent, delay or treat Retinoschisis or eye-related diseases, disorders or conditions are also provided.

Abstract: Methods and compositions are provided for assessing CRISPR/Cas-mediated non-homologous end joining (NHEJ) activity and/or CRISPR/Cas-induced recombination of a target genomic locus with an exogenous donor nucleic acid in vivo or ex vivo. The methods and compositions employ non-human animals comprising a CRISPR reporter such as a genomically integrated CRISPR reporter for detecting and measuring targeted excision of a sequence between two CRISPR/Cas nuclease cleavage sites or disruption of a sequence near a CRISPR/Cas nuclease cleavage site and/or measuring CRISPR/Cas-induced recombination of the CRISPR reporter with an exogenous donor nucleic acid to convert the coding sequence for a first reporter protein to the coding sequence for a different second reporter protein. Methods and compositions are also provided for making and using these non-human animals.

Abstract: Methods for introducing a scarless targeted genetic modification into a preexisting targeting vector are provided. The methods can use combinations of bacterial homologous recombination (BHR) and in vitro assembly to introduce such targeted genetic modifications into a preexisting targeting vector in a scarless manner.

Abstract: This disclosure relates to an animal model of human disease. More specifically, this disclosure relates to a rodent model of mood disorders such as unipolar depression and an anxiety disorder. Disclosed herein are genetically modified rodent animals that carry a humanized G protein-coupled receptor 156 (GPR156) gene that encodes a mutant human GPR156 protein comprising Asp at an amino acid position corresponding to position 533 in a full length wild type human GPR156 protein.

Abstract: Methods and compositions are provided for assessing CRISPR/Cas-mediated non-homologous end joining (NHEJ) activity and/or CRISPR/Cas-induced recombination of a target genomic locus with an exogenous donor nucleic acid in vivo or ex vivo. The methods and compositions employ non-human animals comprising a CRISPR reporter such as a genomically integrated CRISPR reporter for detecting and measuring targeted excision of a sequence between two CRISPR/Cas nuclease cleavage sites or disruption of a sequence near a CRISPR/Cas nuclease cleavage site and/or measuring CRISPR/Cas-induced recombination of the CRISPR reporter with an exogenous donor nucleic acid to convert the coding sequence for a first reporter protein to the coding sequence for a different second reporter protein. Methods and compositions are also provided for making and using these non-human animals.

Abstract: Non-human animals suitable for use as animal models for Retinoschisis are provided. In some embodiments, provided non-human animals are characterized by a disruption in a Retinoschisin-1 locus. In some embodiments, provided non-human animals are characterized by a mutant Retinoschisin-1 gene. The non-human animals may be described, in some embodiments, as having a phenotype that includes the development of one or more symptoms or phenotypes associated with Retinoschisis. Methods of identifying therapeutic candidates that may be used to prevent, delay or treat Retinoschisis or eye-related diseases, disorders or conditions are also provided.