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.

The present invention provides Factor IX fusion proteins with higher specific activity and a longer useful clotting function relative to wild type or non-modified Factor IX protein.

The present invention provides Factor IX fusion proteins with higher specific activity and a longer useful clotting function relative to wild type or non-modified Factor IX protein.

The invention relates to nucleic acid constructs for expression in mice for the production of heavy chain only antibodies and V.sub.H domains, transgenic mice, related methods and uses.

The present disclosure is directed to a method of treating a neuropsychiatric disorder. This method involves selecting a subject having the neuropsychiatric disorder and administering to the selected subject a preparation of glial progenitor cells at a dosage effective to treat the neuropsychiatric disorder in the subject. Another aspect of the disclosure is directed to a method of treating a neuropsychiatric disorder that includes selecting a subject having the neuropsychiatric disorder and administering, to the selected subject, a potassium (K.sup.+) channel activator at a dosage effective to restore normal brain interstitial glial K.sup.+ levels in the selected subject and treat the neuropsychiatric disorder is also disclosed.

A transgenic chicken comprising an inactivated heavy immunoglobulin gene and/or inactivated light chain immunoglobulin gene is provided, as well as cells and targeting vectors for making the same.

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 invention provides a genetically modified non-human animal that comprises in its genome unrearranged T cell receptor variable gene loci, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified non-human animal and methods of making the same. Various methods of using the genetically modified non-human animal are also provided.

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.

Provided herein are methods and agents for modulating the signaling pathway and components thereof that are responsible for assembly and disassembly of synapses in neurons, including amyloid beta (Aβ) mediated synaptotoxicity and synapse loss. Also provided herein are methods for screening and identifying candidate agents capable of modulating synapse formation and (Aβ) mediated synaptotoxicity.