The present disclosure provides compositions with a modulating gene expression and methods for modulating transcription.

Disclosed herein is a recombinant adenovirus genome, said adenovirus genome comprising a heterologous nucleic acid inserted into a cloning site of said genome, said heterologous nucleic acid comprising: (a) a first nucleic acid sequence comprising an adenovirus tripartite sequence (e.g., SEQ ID NO:1) operably linked to a second nucleic acid sequence encoding an interferon (e.g., SEQ ID NO:2); (b) a third nucleic acid sequence comprising a bovine growth hormone polyA termination sequence operably linked to said second nucleic acid sequence (e.g., SEQ ID NO:3); (c) a fourth nucleic acid sequence comprising a porcine elongation factor 1-alpha (EF1α) promoter (e.g., SEQ ID NO:4); (d) a fifth nucleic acid sequence operably linked to said fourth nucleic acid sequence, said fifth nucleic acid sequence encoding a suppressor of cytokine signaling 1 (SOCS1) protein (e.g., SEQ ID NO:5). Furthermore, there is disclosed a method of producing interferon in an animal (e.g., swine).

The present disclosure provides compositions with a modulating gene expression and methods for modulating transcription.

This disclosure relates to methods for screening therapeutic agents to treat altered function of a mutated target gene (e.g., clinical variant) as well as reagents for use in the same.

Among the various aspects of the present disclosure is the provision of engineered cells, animal models, and uses thereof for modeling low grade glioma (LGG). An aspect of the present disclosure provides for a population of cells engineered to silence, downregulate, knock out, or reduce or knock down Cxcl10 expression. Another aspect of the present disclosure provides for an animal engineered to be deficient in Cxcl10, downregulate or reduce expression of Cxcl10, knock out Cxcl10, or knock down Cxcl10 (e.g., Cxcl10.sup.−/− mice). Yet another aspect of the present disclosure provides for a method of growing tumor cell lines or patient-derived xenografts for LGG tumors in an animal (e.g., mouse, rat) including providing a mouse or rat harboring somatic homozygous deletion in the Rag1 or Cxcl10 gene, and implanting an amount of the cells in mice sufficient to grow a tumor.

The present disclosure provides compositions with a modulating gene expression and methods for modulating transcription.

Compositions and methods for the treatment of leukodystrophy, particularly, H-ABC are disclosed.

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.

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.

Provided are non-human animals comprising a mutation in the Fbn1 gene to model neonatal progeroid syndrome with congenital lipodystrophy (NPSCL). Also provided are methods of making such non-human animal models. The non-human animal models can be used for screening compounds for activity in inhibiting or reducing NPSCL or ameliorating NPSCL-like symptoms or screening compounds for activity potentially harmful in promoting or exacerbating NPSCL as well as to provide insights in to the mechanism of NPSCL and potentially new therapeutic and diagnostic targets.