Nonsense-mediated mRNA decay (NMD) polypeptides, nucleic acids encoding NMD polypeptides, and methods of using such polypeptides and nucleic acids in the treatment of ALS and in screening for agents for the treatment of ALS are described.

An expression vector capable of disrupting the silencing of cell cycle genes in adult cells, such as adult cardiac myocytes and other quiescent cells in terminally differentiated tissues, comprising: (a) a nucleic acid sequence encoding lysine-specific demethylase 4D (KDM4D); (b) a promoter that induces or effects overexpression of KDM4D, wherein the promoter is operably linked to the nucleic acid sequence; and (c) a regulatory element that inducibly represses the overexpression of KDM4D. The vector can be administered to a subject in a method for inducing tissue-specific hyperplasia in a mammal, including cardiomyocyte proliferation. The method provides for regenerative therapy, including improving cardiac function after myocardial infarct and other forms of cardiac damage.

Disclosed are methods and compositions for in situ germline genome engineering. The disclosed methods and compositions may be utilized for germline genome engineering in a subject having a reproductive organ containing a fertilized zygote, via: (i) isolating or obtaining the reproductive organ from the subject after a time period following insemination of the subject; (ii) introducing a reagent composition into the reproductive organ, the reagent composition comprising a nuclease system and/or an exogeneous polynucleotide; and (iii) electroporating the reproductive organ.

Provided are a targeting vector, a nucleic acid composition, and a method for constructing a liver-injured mouse model. The targeting vector includes a first expression cassette and a second expression cassette located downstream of the first expression cassette, the first expression cassette has the following elements connected in series in sequence: a liver-specific promoter, a tetracycline transcription activation regulating factor, and a first polyA; and the second expression cassette has the following elements connected in series in sequence: a second polyA, a mouse prourokinase activator encoding gene, and a tetracycline-inducible promoter. The liver-injured mouse model constructed with this targeting vector has the phenotype of spontaneously generating the liver injury and aggravating the liver injury by induction, which provides liver-injured mouse models for studies of liver diseases.

Methods and compositions for monitoring a plurality of independent genomic modifications in cell lineages are provided.

The present invention provides a means for reconstituting tissues and organs having mature functions. A method of preparing a tissue or an organ, comprising coculturing an organ cell with a vascular endothelial cell and a mesenchymal cell, generating an organ bud, transplanting the organ bud into a non-human animal, and then isolating from the non-human animal the transplanted organ bud-derived tissue or organ.

The present invention relates to a use of compounds having TRPV4 inhibitory activity or pharmaceutically acceptable salts thereof, or pharmaceutical compositions containing them for the manufacture of a medicament for preventing or treating a retinal disease accompanied with blood flow disorder or cell disorder. It also relates to a method for preventing or treating the disease, wherein the method comprises administering the compounds or the pharmaceutical compositions containing them to humans or animals. The compounds, the pharmaceutically acceptable salts thereof, or the pharmaceutical compositions containing them may be used in combination with one or more second active agents. The present invention relates to a pharmaceutical composition and a kit containing a compound having TRPV4 inhibitory activity or a pharmaceutically acceptable salt thereof, which is used for preventing or treating the disease. Furthermore, it relates to a marker for diagnosing a disease for which treatment with the compound is useful, and a screening method for drugs in preventing or treating the disease.

Tau reporter compositions, tau reporter cells, and tau reporter animals are provided that comprise a four-repeat (4R) tau isoform linked to a first reporter protein and a three-repeat (3R) tau isoform linked to a second reporter protein that is different from the first reporter protein. Methods are provided for making such tau reporter cells and tau reporter animals and for using such tau reporter cells and tau reporter animals for assessing the activity of tau-targeting reagents.

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 invention relates to expression of the transcription factor Myc and/or pTEF-b and their use as medicaments for inducing proliferation in cells with limited proliferative potential, such as cardiomyocytes. Also described are methods for the prevention and treatment of diseases, such as heart disease, associated with the loss of cells or cell death.