Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN3 RNA in a cell or animal, and in certain embodiments reducing the amount of ATXN3 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include motor dysfunction, aggregation formation, and neuron death. Such neurodegenerative diseases include spinocerebellar ataxia type 3(SCA3).

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.

The invention provides for transgenic donor animals (e.g., pigs) whose cells, tissues and organs have a better long-term survival when transplanted into a human patient. The transgenic donor animal carries one or more human transgenes which is expressed only when the endogenous gene of the donor animal is knocked out shortly before a graft is harvested for transplantation. This “genetic switch” allows the donor animal to remain healthy during the majority of its lifetime, while still allowing expression of the human transgene for optimal transplant tolerance in a human recipient. The transgene may encode a cytokine receptor, an adhesion molecule, or a complement regulatory protein.

Provided is a method for developing a secondary organ by using a non-human animal in which organ formation is inhibited, for the purpose of establishing a process for producing a functional cell such as a β cell within the body of an animal such as a pig, the method including the step of raising a newborn or a fetus of the non-human animal in which organ formation is inhibited by complementing at least a part of the function of the organ whose formation is inhibited.

Disclosed herein are nucleic acids encoding for and proteins expressing chimeric C1q polypeptides, non-human animals comprising said nucleic acids, and methods of making or using said non-human animals.

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.

Provided is a method for developing a secondary organ by using a non-human animal in which organ formation is inhibited, for the purpose of establishing a process for producing a functional cell such as a β cell within the body of an animal such as a pig, the method including the step of raising a newborn or a fetus of the non-human animal in which organ formation is inhibited by complementing at least a part of the function of the organ whose formation is inhibited.

The present invention provides a platform for in vitro or in vivo study of the correlation between a Purkinje cell-specific, circadian clock gene and ataxia, in particular, a non-human transgenic animal model induced by genetic modification to knockdown the circadian clock gene, Bmal1, which causes abnormal diurnality and loss of certain motor skills and learning ability in a subject. The present invention also relates to methods of making and using the platform for various applications. A composition including a vector carrying the Bmal1 gene for restoring expression thereof in the subject's cerebellum to potentially treat ataxia arising from the Bmal1 gene deficiency is also provided.

The present invention concerns non-human animals with cells having a genome that is lacking the entire E3 ubiquitin ligase (Ube3a) gene (including all isoforms and alternative promoters). These animals are useful for modeling Angelman Syndrome. The invention also includes methods for assessing the effect of an agent, such as potential therapeutics, on an animal model by exposing the animal or cells, tissues, or organs isolated therefrom, to an agent of interest.

The present invention relates to: A schizophrenia animal model wherein the model is a mouse in which an anoctamin 1 (ANO1) gene is knocked out in cholinergic neurons of a medial habenula; and a preparation method therefor and the like. The schizophrenia animal model according to the present invention targets the medial habenula which is brain tissue playing a major role in the pathogenesis of schizophrenia, and it has been confirmed that when the ANO1 gene is specifically knocked out in the cholinergic neurons of the medial habenula, positive, negative and cognitive symptoms of schizophrenia are observed, thereby confirming that schizophrenia has been induced. Therefore, the animal model of the present invention is expected to be effectively useful in schizophrenia pathogenesis research and therapeutic agent development and screening.