Genetically modified non-human animals and methods and compositions for making and using the same are provided, wherein the genetic modification comprises a humanization of an endogenous signal-regulatory protein gene, in particular a humanization of a SIRP gene. Genetically modified mice are described, including mice that express a human or humanized SIRP protein from an endogenous SIRP locus.

Genetically modified non-human animals and methods and compositions for making and using the same are provided, wherein the genetic modification comprises a humanization of an endogenous signal-regulatory protein gene, in particular a humanization of a SIRP gene. Genetically modified mice are described, including mice that express a human or humanized SIRP protein from an endogenous SIRP locus.

The present invention relates to a pharmaceutical composition for treating and/or preventing arthritis, which comprising, as an active ingredient, a gene delivery vehicle into which an IK factor or a fragment thereof, or a nucleic acid encoding thereof is inserted. IK factor or the fragment thereof, and the nucleic acid encoding thereof, which are the active ingredient of the pharmaceutical composition according to the present invention, are derived from an organism and therefore, show no side effects in administered into a subject for a long time. Accordingly, they ensures safety and are expected to effectively treat arthritis by being involved in the upstream mechanism for suppressing arthritis.

Methods and compositions are described for making phenotypically female fertile animals from XY donor cells and suitable host embryos. Culture media and methods are provided for maintaining XY donor cells in culture that after introduction into a host embryo and gestation in a suitable host will result in fertile XY female animals. Methods and compositions are described for making fertile female animals in an F0 generation from a donor XY cell and a host embryo, as are methods for making F1 progeny that are homozygous for a modification from a heterozygous F0 fertile male and a heterozygous F0 fertile female sibling.

The present invention relates to a pharmaceutical composition for treating and/or preventing arthritis, which comprising, as an active ingredient, a gene delivery vehicle into which an IK factor or a fragment thereof, or a nucleic acid encoding thereof is inserted. IK factor or the fragment thereof, and the nucleic acid encoding thereof, which are the active ingredient of the pharmaceutical composition according to the present invention, are derived from an organism and therefore, show no side effects in administered into a subject for a long time. Accordingly, they ensures safety and are expected to effectively treat arthritis by being involved in the upstream mechanism for suppressing arthritis.

The invention provides a compound capable of inhibiting ubiquitination for use in treating a disorder or symptom associated with reduced dystroglycan function in a subject.

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.

Genetically modified non-human animals and methods and compositions for making and using the same are provided, wherein the genetic modification comprises a humanization of an endogenous signal-regulatory protein gene, in particular a humanization of a SIRP gene. Genetically modified mice are described, including mice that express a human or humanized SIRP protein from an endogenous SIRP locus.

Methods and compositions are described for making phenotypically female fertile animals from XY donor cells and suitable host embryos. Culture media and methods are provided for maintaining XY donor cells in culture that after introduction into a host embryo and gestation in a suitable host will result in fertile XY female animals. Methods and compositions are described for making fertile female animals in an F0 generation from a donor XY cell and a host embryo, as are methods for making F1 progeny that are homozygous for a modification from a heterozygous F0 fertile male and a heterozygous F0 fertile female sibling.

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.