Provided is an invention based, in part, on novel gene constructs that encode a microdystrophin protein for use in gene therapy. The microdystrophin gene constructs and expression cassettes were engineered for improved therapy with respect to efficacy, potency and safety to the subject when expressed by a viral vector in muscle cells and/or CNS cells.

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.

The present invention describes transgenic animals with human(ized) immunoglobulin loci and transgenes encoding human(ized) Igα and/or Igβ sequences. Of particular interest are animals with transgenic heavy and light chain immunoglobulin loci capable of producing a diversified human(ized) antibody repertoire that have their endogenous production of Ig and/or endogenous Igα and/or Igβ sequences suppressed. Simultaneous expression of human(ized) immunoglobulin and human(ized) Igα and/or Igβ results in normal B-cell development, affinity maturation and efficient expression of human(ized) antibodies.

Disclosed are fish with impaired reproductive capacity and methods and compositions for producing the same. The reproductively impaired fish may include catfish, such as Ictalurus punctatus. The disclosed methods may be generally useful for mitigating environmental impact of escaped genetically engineered fish.

Compositions and methods for improving embryo development, treating idiopathic male factor infertility, and enabling infertile/sub-fertile/sterile men to father their own genetic offspring are provided. Typically, the methods include administering into a male or female gamete or fertilized embryo an effective amount of a compound that increases bioavailability of a TET protein to improve development of an embryo resulting from fertilization of the female gamete by a male gamete. The compound can be administered into the gamete or embryo before, during, or after fertilization. The compound can be administered by an injection such as intracytoplasmic injection. The compound and the male gamete can be administered in combination by intracytoplasmic sperm injection. Methods of making male gametes, and methods of modifying the genome of a male gamete or embryo using an effective amount of a gene editing composition to correct a gene mutation or anomaly in the genome thereof are also provided.

Described herein are rats with a hepatic deficiency comprising decreased function, activity, or expression of an enzyme in the tyrosine catabolic pathway (such as fumarylacetoacetate hydrolase), and methods of using the same for in vivo engraftment and expansion of heterologous hepatocytes, such as human hepatocytes, analysis of human liver disease, and analysis of xenobiotics. Also disclosed is the use of immunodeficient rats for the engraftment and expansion of heterologous hepatocytes.

Artificial expression constructs for selectively modulating gene expression in selected central nervous system cell types are described. The artificial expression constructs can be used to selectively express synthetic genes or modify gene expression in GABAergic neurons generally; and/or GABAergic neuron cell types such as lysosomal associated membrane protein 5 (Lamp5) neurons; vasoactive intestinal polypeptide-expressing (Vip) neurons; somatostatin (Sst) neurons; and/or parvalbumin (Pvalb) neuron cell types. Certain artificial expression constructs additionally drive selective gene expression in Layer 4 and/or layer 5 intratelencephalic (IT) neurons, deep cerebellar nuclear neurons or cerebellar Purkinje cells.

The disclosure relates, in some aspects, to compositions and methods for treatment of central nervous system (CNS) diseases, for example Parkinson's disease (PD) and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding one or more CNS disease-associated gene products and/or one or more an inhibitory nucleic acids targeting a CNS disease-associated gene or gene product. In some embodiments, the disclosure provides methods of treating CNS diseases by administering such expression constructs to a subject in need thereof.

The present disclosure relates to a transgenic non-human mammal (e.g., mouse) that expresses a common light chain, wherein the transgenic non-human mammal comprises a hybrid light chain locus from which a light chain having a human Vκ joined to a mouse Jκ is expressed. Also provided are methods of making a transgenic non-human mammal capable of expressing a common light chain.

The present invention relates to transgenic ornamental barbs, as well as methods of making such fish by in vitro fertilization techniques. Also disclosed are methods of establishing a population of such transgenic barbs and methods of providing them to the ornamental fish industry for the purpose of marketing.