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 relates to transgenic mice and isolated transgenic mouse cells, the mice and mouse cells comprising a disrupted H2 class I gene, a disrupted H2 class II gene, a functional HLA class I transgene, and a functional HLA class II transgene. In embodiments, the transgenic mouse or mouse cells are deficient for both H2 class I and class II molecules, wherein the transgenic mouse comprises a functional HLA class I transgene and a functional HLA class II transgene. In embodiments, the transgenic mouse or mouse cell has the genotype HLA-A2.sup.+HLA-DR1.sup.+2mIA. The invention also relates to methods of using a transgenic mouse of the invention.

The invention relates to the development of an animal model for testing various agents in the treatment of a clotting disorder. More specifically, the invention relates to the use of ultra-large molecular weight multimers of von Willebrand factor (VWF) in various mouse strains to induce thrombotic thrombocytopenic purpura (TTP)-like symptoms for the development of a mouse model of TTP. The invention also provides methods for generating such animal disease models and screening methods for identifying biologically active compounds which are effective in the treatment of TTP.

Provided herein are gene therapy methods for the treatment of mucopolysaccharidosis type IVA (MPS IVA) involving the use of recombinant adeno-associated viruses (rAAVs) to deliver human N-acetylgalactosamine-6-sulfate sulfatase (hGALNS) to the bone of a human subject diagnosed with MPS IVA. Also provided herein are rAAVs that can be used in the gene therapy methods and methods of making such rAAVs.

Methods of normalizing bile acid production in a mouse engrafted with human hepatocytes by the administration of human FGF19 are disclosed. Also disclosed is a transgenic host animal, such as a mouse, that expresses human FGF19 that has normalized bile acid production when engrafted with human hepatocytes.

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.

The present disclosure provides reagents and methods for treating disease using modified immune cells (e.g., T cell comprising CAR or TCR) in combination with an agent associated with induction of immunogenic cell death (ICD) and optionally further in combination with an agent that specifically binds to and/or inhibits an immune suppression component and/or an agonist of an immune stimulatory molecule.

The present application relates to an animal or cell having a myostatin gene in which 12 base pairs of the second exon are deleted. The present application may also comprise a composition capable of manipulating the deletion of 12 base pairs of a myostatin gene to construct the animal or the cell. The present application also relates to use of the composition for increasing muscle.

The present invention is directed to genetic manipulation of neural cells in the gyrencephalic fetal brain for developing treatment strategies for various neurodevelopmental disorders.

The present invention provides a method for promoting sexual maturation of fish, the method including a step of suppressing functional expression of at least one of a leptin receptor and a leptin of the fish. An object of the present invention is to provide the method for promoting the sexual maturation of the fish in order to obtain individuals of fish capable of ovulation or spermiation at one year of age at a higher rate than in nature or under normal aquaculture conditions.