Provided herein are methods, compositions and transgenic mice useful in treating and developing treatments for VCP-associated neurodegenerative diseases.

This document relates to methods and materials involved in the removal of senescent cells within a mammal. For example, transgenic non-human animals that can be induced to delete senescent cells are provided.

It was found that bacteria belonging to the genus Clostridium induce accumulation of regulatory T cells (Treg cells) in the colon. Moreover, the present inventors found that regulatory T cells (Treg cells) induced by from these bacteria suppressed proliferation of effector T-cells. From these findings, the present inventors found that the use of bacteria belonging to the genus Clostridium or a physiologically active substance derived therefrom made it possible to induce proliferation or accumulation of regulatory T cells (Treg cells), and further to suppress immune functions.

It was found that bacteria belonging to the genus Clostridium induce accumulation of regulatory T cells (Treg cells) in the colon. Moreover, the present inventors found that regulatory T cells (Treg cells) induced by from these bacteria suppressed proliferation of effector T-cells. From these findings, the present inventors found that the use of bacteria belonging to the genus Clostridium or a physiologically active substance derived therefrom made it possible to induce proliferation or accumulation of regulatory T cells (Treg cells), and further to suppress immune functions.

A genetically modified rodent is provided that comprises a modified Acvr1 gene that comprises a conditional altered exon 7 encoding R258G in antisense orientation, flanked by site-specific recombinase recognition sites, wherein the altered exon is inverted to sense orientation upon action of a recombinase, resulting in ectopic bone formation.

The present invention relates to a method of producing an inducible animal model of stress comprising genetically modifying a non-human vertebrate to express one or more protein(s) that can be activated by light in (a) cell(s) of the hypothalamic-pituitary-adrenal axis, wherein the protein(s) that can be activated by light are capable of inducing the release of (i) corticotrophin-releasing hormone (CRH) and/or arginine-vasopressin (A VP) from neurons in the paraventricular nucleus of the rostral hypothalamus; (ii) adrenocorticotropic hormone (ACTH) from corticotroph cells in the anterior pituitary; and/or (iii) glucocorticoids from cells in the adrenal cortex. The present invention further relates to an animal model of stress obtained by the method of the invention and the use of said animal model for screening for a compound for preventing, ameliorating or treating stress and/or stress-associated diseases. Further, the present invention also relates to a method of screening for a compound for preventing, ameliorating and/or treating stress and/or stress-associated diseases and methods of analyzing stress behavior in fish.

A genetically modified mouse is provided that comprises a conditional Acvr1 allele that comprises a mutated exon that, upon induction, converts to a mutant exon phenotype, wherein the mutant exon phenotype includes ectopic bone formation. Mice comprising a mutant Acvr1 exon 5 in antisense orientation, flanked by site-specific recombinase recognition sites, are provided, wherein the mice further comprise a site-specific recombinase that recognizes the site-specific recombinase recognitions sites, wherein the recombinase is induced upon exposure of the mouse to tamoxifen. Upon exposure to tamoxifen, the recombinase is expressed and acts on the RRS-flanked mutant exon 5 and places the mutant exon 5 in sense orientation and deletes the wild-type exon.

Disclosed are materials and methods for creating customizable traits in animals. In the demonstration of the principle of the subject invention, a keratin-14 specific promoter is used with, red fluorescent protein in the loxp cassette, dominant black (G23) beta defensin 103 in the pigment cassette, and an SV40 (with intron) polyadenylation sequence. When Cre recombinase (or HTNCre) is applied to the animal's skin in a carrier base (e.g., lipid bilayers), fur is permanently genetically modified to turn black in the shape in which it was applied.

This document relates to methods and materials involved in the removal of senescent cells within a mammal. For example, transgenic non-human animals that can be induced to delete senescent cells are provided.

The present invention relates to an autoimmune disease animal model and a method for preparing the same. The animal model of the present invention efficiently generates an autoantibody that causes autoimmune disease, by introducing an autoantigen-encoding gene through the Cre-LoxP system, which enables stable and continuous expression of the autoantigen at a desired time by treatment of Cre recombinase. Contrary to the conventional method that fails to effectively produce autoantibody due to leaky expression and immune tolerance, or requires repeated administration over several weeks, the present invention achieves sustainable expression of an effective amount of autoantigen by only one TAT-Cre recombinase treatment, thus may be utilized as an outstanding animal model reproducing various symptoms and molecular mechanisms of autoimmune diseases.