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.

The present disclosure provides transgenic nematode systems for assessing function of heterologous genes, their variants and drug discovery. The transgenic nematodes contain a heterologous gene that is inserted via homologous recombination at the native locus replacing and removing the nematode ortholog, wherein expression of the heterologous gene rescues function of the removed nematode ortholog and a transgenic control animal is provided. The heterologous gene may be further modified to provide a variant, such as a human clinical variant, whereby a transgenic test animal is provided. Those transgenic test animals are used in methods to assess function of the heterologous variant and drug screens to find therapeutic candidates reversing deviant activity back to wildtype.

The present disclosure provides a microfluidic device and system for measuring a composite electropharyngeogram (EPG) signal from a pool of multiple nematodes, wherein the composite EPG signal is measured from the pool of nematodes present in a single recording channel connected to two or more integrated electrodes. The microfluidic device includes an inlet port and outlet port directly connected to a single recording channel and two or more electrodes directly connected to the recording channel. The recording channel is configured to hold 10 to 10,000 nematodes.

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.

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.

The present disclosure provides transgenic non-human animal (e.g., nematode) systems for assessing heterologous polygenic or monogenic phenotypes, their variants and drug discovery. The transgenic non-human animals (e.g., nematodes) contain a first heterologous polypeptide coding sequence and a second heterologous polypeptide coding sequence (a plurality of heterologous polypeptide coding sequences), wherein the first and second heterologous polypeptide coding sequences are integrated into the host animal genome, and wherein expression of the first and second heterologous polypeptide coding sequence contribute to the heterologous phenotype. The plurality of heterologous polypeptide coding sequences are interrelated wherein their expression products, directly or indirectly, contribute or lead to an observable phenotype.

This document relates to methods and materials involved in the deconvolution of serum. For example, transgenic non-human animals (e g , transgenic mice) that secrete tagged (e.g., biotinylated) molecules from a particular tissue are provided.

The present disclosure relates to nucleic acid promoter sequences that are able to specifically express genes operatively linked to the promoter in brainstem and spinal motor neuron cells, and to methods for using such promoters to selectively express genes in motor neurons in vitro and in vivo. It is based, at least in part, on the discovery that the nucleic acid of SEQ ID NO: 1 functioned as a motor neuron-specific promoter and was successful in expressing transgenes in motor neuron cells in vivo. The present disclosure also relates to compositions that can increase the activity or expression level of miR-218 and to compositions that can decrease the expression of miR-218 target nucleic acids.

This disclosure relates to methods for screening therapeutic agents to treat altered function of a mutated target gene (e.g., clinical variant) as well as reagents for use in the same.

Provided herein are compositions comprising light-activated chimeric proteins expressed on plasma membranes and methods of using the same to selectively depolarize excitatory or inhibitory neurons.