The present disclosure provides a genetically modified mouse comprising a genomic nucleic acid encoding human APOE4, a genomic nucleic acid encoding mouse TREM2 modified to include a R47H substitution, and at least one genomic modification selected from the group consisting of: (a) a genomic nucleic acid encoding mouse ABCA7 modified to include an A 1541 G substitution; (b) a genomic nucleic acid encoding mouse APP modified to include G60IR, F606Y, and R609H substitutions; (c) a genomic nucleic acid encoding mouse PLCG2 modified to include a M28L substitution; (d) a genomic nucleic acid encoding mouse MTHFR modified to include a A262V substitution; (e) an inactivated Ceacaml allele; and (f) an inactivated II1rap allele. Methods of producing the genetically modified mouse and methods of using the genetically modified mouse are also provided.

The present disclosure relates to genetically modified non-human animals expressing human or chimeric (e.g., humanized) Thrombopoietin (THPO), and methods of use thereof.

It is shown that ventral hippocampal kindling results in functional reorganization of the ventral hippocampal excitatory circuits. Most pronounced is the connectivity to the medial prefrontal cortex, with increased volume of activation on fMRI and increased amplitude of activation on electrophysiology. There is evidence of increased anxiety following kindling Methods are provided for simultaneous LFP-fMRI to image single seizures Imaging the spatiotemporal dynamics of individual seizures enables characterization of propagation patterns of focal and secondary-generalized seizures, that provide for targeted intervention.

Provided herein, in some embodiments, are methods and compositions for the treatment of Charcot-Marie-Tooth disease.

The present invention relates to a method for screening an anticancer agent by causing drosophila having the characteristics of a) expression of mutant Ras85D, b) deletion or suppressed expression of a p53 gene, c) overexpression of a cyclin E gene, and d) deletion or suppressed expression of a Med gene to ingest a test substance and comparing the survival rate thereof with the survival rate of drosophila that did not ingest the test substance. The present invention also relates to a combination drug of at least two kinase inhibitors for treatment of pancreatic cancer and to kinase inhibitors for use in said combination drug.

Transgenic non-human animal models for cellular senescence are provided herein, as are methods and materials for making and using the transgenic non-human animal models. For example, a p21-Cre mouse model for cellular senescence is provided herein.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) IL10R and/or a human or chimeric (e.g., humanized) IL10, and methods of use thereof.

This disclosure relates to genetically modified immunodeficient animals which express a human or chimeric (e.g., humanized) SIRPα and/or human or chimeric (e.g., humanized) CD47, and methods of use thereof.

Provided herein are high-throughput methods for genetic barcoding and analysis, e.g., for tagging each biomaterial apsule with a barcode cell. These barcode cells are derived from patient samples, and thus embody natural human genetic variation. Also provided are SNP panels that can be used as genetic barcodes to identify the identity of a cell.

The invention relates to animal models, and in particular to novel in vivo animal models for neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease or Motor Neurone Disease. The invention extends to methods for providing such models. The invention also provides animal models per se and methods for investigating the underlying mechanisms occurring in such neurodegenerative disorders, in particular, Alzheimer's disease, and also extends to models, methods and assays for testing pharmacological test compounds, which may modulate neurological processes, and for drug screening for use in treating neurodegenerative diseases.