This disclosure relates to a genetically modified rodent and use thereof as a rodent model. More specifically, this disclosure relates to rodent (e.g., mouse or rat) comprising a loss of function mutation in an endogenous Crnn (cornulin) gene, and to use of such a rodent animal as a rodent model of skin inflammation disorders (e.g., psoriasis).

Embodiments of the present disclosure pertain to methods of treating or preventing Alzheimer's disease or symptoms of Alzheimer's disease in a subject by administering to the subject an active agent that includes an adenovirus-36 E4orf1 protein, a nucleic acid encoding an adenovirus-36 E4orfl protein, or combinations thereof. Additional embodiments of the present disclosure pertain to the active agents of the present disclosure for use in the treatment or prevention of Alzheimer's disease or symptoms of Alzheimer's disease.

Artificial expression constructs for selectively modulating gene expression in selected central nervous system cell types are described. The artificial expression constructs can be used to selectively express synthetic genes or modify gene expression in GABAergic neurons generally; and/or GABAergic neuron cell types such as lysosomal associated membrane protein 5 (Lamp5) neurons; vasoactive intestinal polypeptide-expressing (Vip) neurons; somatostatin (Sst) neurons; and/or parvalbumin (Pvalb) neuron cell types. Certain artificial expression constructs additionally drive selective gene expression in Layer 4 and/or layer 5 intratelencephalic (IT) neurons, deep cerebellar nuclear neurons or cerebellar Purkinje cells.

Provided herein non-human transgenic animals comprising a genome that: i) under-expresses, or is inducible to under-express, Hu Antigen R (HuR) in at least some neurons of said transgenic animal; ii) does not express HuR, or is inducible to not express HuR, in at least some neurons of said transgenic animal; or iii) does not express functional HuR, or is inducible to not express functional HuR in at least some neurons of said transgenic animal, as well as methods of screening drugs and therapies (e.g., useful in treating ALS) using such animals.

The present disclosure is directed to transgenic animals (e.g., transgenic porcine animals) comprising multiple genetic modifications that advantageously render these animals suitable donors for xenotransplanation. The present disclosure extends to organs, organ fragments, tissues and cells derived from these animals and their therapeutic use. The present disclosure further extends to methods of making such animals. In certain embodiments, the transgenic animals (e.g., transgenic porcine animals) have reduced expression of the growth hormone receptor (GHR) gene or have impaired function of the GHR protein.

The invention provides for transgenic donor animals (e.g., pigs) whose cells, tissues and organs have a better long-term survival when transplanted into a human patient. The transgenic donor animal carries one or more human transgenes which is expressed only when the endogenous gene of the donor animal is knocked out shortly before a graft is harvested for transplantation. This “genetic switch” allows the donor animal to remain healthy during the majority of its lifetime, while still allowing expression of the human transgene for optimal transplant tolerance in a human recipient. The transgene may encode a cytokine receptor, an adhesion molecule, or a complement regulatory protein.

The invention provides a Noctuid dsx splice cassette for expression of a gene of interest on a sex-specific basis, gene expression systems for imparting a self-limiting trait to transformed Noctuidae, as well as transgenic Noctuidae and methods of suppressing populations of Noctuidae and reducing, inhibiting or eliminating crop damage caused by the Noctuid insects.

The present invention relates to microglial or myeloid expressed Alzheimer's disease associated (ME-AD) gene reporter constructs, cell lines and transgenic animals and their use for identifying agents that modulate the level or expression of ME-AD genes.

Described herein are methods of producing transgenic Bombyx mori by targeting and modifying genomic regions associated with sericin proteins. Embodiments include vectors utilized for modifying one or more sericin genes. Embodiments include plasmid constructs utilized for molecular cloning of donor sequences configured for replacement of or insertion into a targeted sericin gene and utilized for transfection of Bombyx mori with the donor sequences. Embodiments include transgenic Bombyx mori that have been transfected with the donor sequences and are capable of producing a non-native protein product with minimized or prevented production of sericin.

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.