Non-human animals comprising a human or humanized IL-4 and/or IL-4R nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous IL-4 gene and/or IL-4R gene with a human IL-4 gene and/or IL-4R gene in whole or in part, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized IL-4 gene under control of non-human IL-4 regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4-encoding sequence with human IL-4-encoding sequence at an endogenous non-human IL-4 locus. Non-human animals comprising a human or humanized IL-4R, gene under control of non-human IL-4R regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4R-encoding sequence with human or humanized IL-4R-encoding sequence at an endogenous non-human CIL-4R locus. Non-human animals comprising human or humanized IL-4 gene and/or IL-4R, sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

[Problem] The objectives of the present invention are to provide a method for making an animal that has been stressed, in particular, chronically stressed, affect or develop a specific disease or symptom, and, through elucidating the process from loading stress to affection or onset of the disease or symptom, to provide a useful tool for research and development of preventing or treating methods of the disease or symptom. [Solution] The present invention relates to a method for producing a disease modeling non-human animal having cerebrovascular inflammation, the disease modeling non-human animal, a method for screening a drug using the disease modeling non-human animal, a method for determining the risk of a disease using the presence of cerebrovascular inflammation as an indicator, and a pharmaceutical for preventing and/or treating progressive multiple sclerosis or the like. The present invention enables developing pharmaceuticals for the above described diseases or the like and performing researches for elucidating their pathogenic mechanisms. The present invention also enables determining the risk of affection or onset of progressive multiple sclerosis or the like and preventing and/or treating progressive multiple sclerosis or the like.

Non-human animals comprising a human or humanized C3 and/or C5 nucleic acid sequence are provided as well as methods for using the same to identify compounds capable of modulating the complement system. Non-human animals that comprise a replacement of the endogenous C5 gene and/or C3 gene with a human or humanized C5 gene and/or C3 gene, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized C5 gene under control of non-human C5 regulatory elements is also provided, including non-human animals that have a replacement of non-human C5-encoding sequence with human C5-encoding sequence at an endogenous non-human C5 locus. Non-human animals comprising a human or humanized C3 gene under control of non-human C3 regulatory elements is also provided, including non-human animals that have a replacement of non-human C3 protein-encoding sequence with human or humanized C3 protein-encoding sequence at an endogenous non-human C3 locus. Non-human animals comprising human or humanized C3 and/or C5 sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

The present invention aims to provide: an immunostimulant useful for maintaining, enhancing or suppressing an immune function associated with CD300a activation signaling, or an immunomodulator as an immunosuppressant useful for suppressing the immune function; use of a CD300a gene-deficient mouse for pathology analysis and the like; an anti-CD300a antibody; and the like.

Non-human animals comprising a human or humanized IL-4 and/or IL-4R nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous IL-4 gene and/or IL-4R gene with a human IL-4 gene and/or IL-4R gene in whole or in part, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized IL-4 gene under control of non-human IL-4 regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4-encoding sequence with human IL-4-encoding sequence at an endogenous non-human IL-4 locus. Non-human animals comprising a human or humanized IL-4R gene under control of non-human IL-4R regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4R-encoding sequence with human or humanized IL-4R-encoding sequence at an endogenous non-human C IL-4R locus. Non-human animals comprising human or humanized IL-4 gene and/or IL-4R sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

The present invention provides an antibody to a fibrosis-related molecule and medical application thereof. The antibody of the present invention is an antibody that binds to CHL1 protein and an antibody that neutralizes the binding of the CHL1 protein to a fibroblast.

This disclosure relates to genetically modified rodent animals and rodent models of human diseases. More specifically, this disclosure relates to genetically modified rodents whose genome comprises a humanized Il1rl2 gene (coding for the IL1rl2 subunit of the IL-36R protein) and human IL-36, and ligand genes. The genetically modified rodents disclosed herein display enhanced skin and intestinal inflammation as a preclinical model of psoriasis and IBD, respectively, and serve as a rodent model of human DITRA disease.

Non-human animals comprising a human or humanized C3 and/or C5 nucleic acid sequence are provided as well as methods for using the same to identify compounds capable of modulating the complement system. Non-human animals that comprise a replacement of the endogenous C5 gene and/or C3 gene with a human or humanized C5 gene and/or C3 gene, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized C5 gene under control of non-human C5 regulatory elements is also provided, including non-human animals that have a replacement of non-human C5-encoding sequence with human C5-encoding sequence at an endogenous non-human C5 locus. Non-human animals comprising a human or humanized C3 gene under control of non-human C3 regulatory elements is also provided, including non-human animals that have a replacement of non-human C3 protein-encoding sequence with human or humanized C3 protein-encoding sequence at an endogenous non-human C3 locus. Non-human animals comprising human or humanized C3 and/or C5 sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

This invention provides methods of treating androgenetic alopecia (AGA), acne, rosacea, prostate cancer, and benign prostatic hypertrophy (BPH), comprising the step of contacting a subject with a compound or composition capable of decreasing prostaglandin D2 (PGD2) level or activity, a downstream signaling or receptor pathway thereof, or prostaglandin D2 synthase level or activity; methods of stimulating hair growth, comprising the step of contacting a subject with a compound or composition capable of increasing or decreasing the activity or level of a target gene of the present invention, or with a protein product of the target gene or an analogue or mimetic thereof; and methods of testing for AGA and evaluating therapeutic methods thereof, comprising measuring PGD2 levels.

A non-human animal or a part of the same in which the function of Mipep gene is totally or partially lost in adipose tissues or the expression level of Mipep gene in adipose tissues is lowered compared to a wild type; and mesenchymal stem cells or adipocytes in which the function of Mipep gene is totally or partially lost or the expression level of Mipep gene is lowered compared to a wild type. A therapeutic or prophylactic drug that includes the mesenchymal stem cells or adipocytes or a culture supernatant thereof; and a method for preparing a mitokine mixture using the non-human cells, mesenchymal stem cells or adipocytes.