The present disclosure provides immunodeficient mouse models that comprise a nucleic acid encoding a human or humanized amyloid precursor protein (APP) and, in some models, further comprise a nucleic acid encoding a mutated human presenilin 1 protein (PSEN1). These mouse models are useful, for example, for Alzheimer's disease studies.

The invention relates to a long DH (LDH) cassette comprising a recombinant DH construct comprising at least two DH gene segments encoding at least 10 amino acids of the HCDR3 amino acid sequence, wherein at least one of the DH gene segments is a heterologous DH gene segment; an immunoglobulin heavy chain locus and a transgenic non-human animal comprising the same; and their use in producing an immunoglobulin library with long HCDR3 regions.

A method is provided of producing chimeric embryos and animals with exclusively donor-derived germ cells. Inactivation of a primordial germ cell specification gene results in the loss of primordial germ cells, the precursor cells for future sperm and egg, and in total loss of the endogenous germline. When complemented with embryonic cells from a desired donor, the resulting surrogate animal has all the resulting germline, and subsequent spermatogenesis, of the donor.

Described herein is a genetically modified plant or non-human animal having reduced expression of an endogenous target gene.

The present invention relates to a human artificial chromosome which is genetically transmissible to the next generation with high efficiency and the method for using the same. More specifically, the present invention relates to: a human artificial chromosome in which an about 3.5 Mb to about 1 Mb region containing an antibody light chain gene derived from human chromosome 22 is bound to a chromosome fragment which is transmissible to a progeny through a germ line of a non-human animal, said chromosome fragment is derived from another human chromosome; a non-human animal carrying the human artificial chromosome and an offspring thereof; a method for producing the non-human animal; a method for producing a human antibody using the nonhuman animal or an offspring thereof; and a human antibody-producing mouse carrying the human artificial chromosome.

The present invention pertains to a non-human genetically modified animal with increased susceptibility to infection with a human virus. The invention suggests to genetically impair the expression of newly identified viral infection repression factors CD302, Cr11, Ndufc2, AW112010, Scarb2 and Zc3hav1, which markedly improves infection with human viruses in none-human hosts. Furthermore provided are methods for the generation of the animal of the invention, methods for increasing or reducing the susceptibility of a cell to viral infection, methods for screening novel modulators of viral infection as well as new therapy options for the treatment of viral diseases, in particular hepatitis C.

Opsin proteins are GPCRs known for light perception. Here it is shown that these receptors are also expressed in chemosensory cells and function as chemosensory receptors activated by a range of molecules, including tastants such as theobromine, for which a receptor has not previously been known. Provided are novel assay systems for assessing chemosensory opsin activation by chemical ligands. By these assays, novel ligands of chemosensory opsins may be identified, the chemosensory properties of molecules may be evaluated; and the modulation of chemosensory properties by modifications or modulators may be tested.

Human or humanized tissues and organs suitable for transplant are disclosed herein. Gene editing of a host animal provides a niche for complementation of the missing genetic information by donor stem cells. Editing of a host genome to knock out or debilitate genes responsible for the growth and/or differentiation of a target organ and injecting that animal at an embryo stage with donor stem cells to complement the missing genetic information for the growth and development of the organ. The result is a chimeric animal in which the complemented tissue (human/humanized organ) matches the genotype and phenotype of the donor. Such organs may be made in a single generation and the stem cell may be taken or generated from the patient's own body. As disclosed herein, it is possible to do so by simultaneously editing multiple genes in a cell or embryo creating a niche for the complemented tissue. Multiple genes can be targeted for editing using targeted nucleases and homology directed repair (HDR) templates in vertebrate cells or embryos.

This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.

Described herein are compositions (e.g. cells and transgenic animals) and methods relating to engineered Ig loci that permit expression of particular antibodies or antibody segments while still permitting recombination and/or maturation process for antibody optimization.