Abstract: Disclosed herein are compositions and methods for deleting or duplicating DNA in a mammalian genome. Also disclosed are compositions and methods for generating a random genome-wide chromosome rearrangement. Also disclosed are compositions and methods for streamlined construction of gene targeting vectors.

Abstract: Synovial sarcoma is an aggressive soft-tissue malignancy. Disclosed herein is an animal model of synovial sarcoma wherein one or more myogenic cells of the animal express recombinant SYT-SSX fusion polypeptide. Using this model, myoblasts were identified as a source of synovial sarcoma. Remarkably, within the skeletal muscle lineage, while expression of the oncoprotein in immature myoblasts leads to induction of synovial sarcoma with 100% penetrance, its expression in more differentiated cells induces myopathy without tumor induction. In addition, early widespread expression of the disclosed fusion protein disrupts normal embryogenesis, causing lethality.

Abstract: Disclosed herein are compositions and methods for deleting or duplicating DNA in a mammalian genome. Also disclosed are compositions and methods for generating a random genome-wide chromosome rearrangement. Also disclosed are compositions and methods for streamlined construction of gene targeting vectors.

Abstract: This invention provides in vivo and in vitro methods of screening for an agent or a combination of agents that reduces one or more repetitive behaviors, comprising contacting neuronal cells of an animal with a HOXB8 gene mutation with the agent combination of agents to be screened, and determining whether one or more repetitive behaviors of the animal is reduced or whether one or more biochemical correlates of repetitive behaviors is reduced, the reduction in one or more repetitive behaviors or biochemical correlates indicating an agent or combination of agents that reduces repetitive behaviors. The invention also provides method of treating a subject with repetitive behaviors, comprising administering a therapeutically effective dose of the agent or combination of agents identified by the screening method.

Abstract: A method of obtaining and the resulting isolated progenitor or stem cell population of proliferating cells persistently expressing a candidate molecule. Further, novel methods of ex vivo gene product (e.g., protein) production and treating symptoms of neurological or neurodegenerative disorders are also provided.

Abstract: This invention provides in vivo and in vitro methods of screening for an agent or a combination of agents that reduces one or more repetitive behaviors, comprising contacting neuronal cells of an animal with a HOXB8 gene mutation with the agent combination of agents to be screened, and determining whether one or more repetitive behaviors of the animal is reduced or whether one or more biochemical correlates of repetitive behaviors is reduced, the reduction in one or more repetitive behaviors or biochemical correlates indicating an agent or combination of agents that reduces repetitive behaviors. The invention also provides method of treating a subject with repetitive behaviors, comprising administering a therapeutically effective dose of the agent or combination of agents identified by the screening method.

Abstract: Positive-negative selector (PNS) vectors are provided for modifying a target DNA sequence contained in the genome of a target cell capable of homologous recombination. The vector comprises a first DNA sequence which contains at least one sequence portion which is substantially homologous to a portion of a first region of a target DNA sequence. The vector also includes a second DNA sequence containing at least one sequence portion which is substantially homologous to another portion of a second region of a target DNA sequence. A third DNA sequence is positioned between the first and second DNA sequences and encodes a positive selection marker which when expressed is functional in the target cell in which the vector is used. A fourth DNA sequence encoding a negative selection marker, also functional in the target cell, is positioned 5′ to the first or 3′ to the second DNA sequence and is substantially incapable of homologous recombination with the target DNA sequence.

Abstract: Positive-negative selector (PNS) vectors are provided for modifying a target DNA sequence contained in the genome of a target cell capable of homologous recombination. The vector comprises a first DNA sequence which contains at least one sequence portion which is substantially homologous to a portion of a first region of a target DNA sequence. The vector also includes a second DNA sequence containing at least one sequence portion which is substantially homologous to another portion of a second region of a target DNA sequence. A third DNA sequence is positioned between the first and second DNA sequences and encodes a positive selection marker which when expressed is functional in the target cell in which the vector is used. A fourth DNA sequence encoding a negative selection marker, also functional in the target cell, is positioned 5′ to the first or 3′ to the second DNA sequence and is substantially incapable of homologous recombination with the target DNA sequence.

Abstract: Positive-negative selector (PNS) vectors are provided for modifying a target DNA sequence contained in the genome of a target cell capable of homologous recombination. The vector comprises a first DNA sequence which contains at least one sequence portion which is substantially homologous to a portion of a first region of a target DNA sequence. The vector also includes a second DNA sequence containing at least one sequence portion which is substantially homologous to another portion of a second region of a target DNA sequence. A third DNA sequence is positioned between the first and second DNA sequences and encodes a positive selection marker which when expressed is functional in the target cell in which the vector is used. A fourth DNA sequence encoding a negative selection marker, also functional in the target cell, is positioned 5' to the first or 3' to the second DNA sequence and is substantially incapable of homologous recombination with the target DNA sequence.

Abstract: Positive-negative selector (PNS) vectors are provided for modifying a target DNA sequence contained in the genome of a target cell capable of homologous recombination. The vector comprises a first DNA sequence which contains at least one sequence portion which is substantially homologous to a portion of a first region of a target DNA sequence. The vector also includes a second DNA sequence containing at least one sequence portion which is substantially homologous to another portion of a second region of a target DNA sequence. A third DNA sequence is positioned between the first and second DNA sequences and encodes a positive selection marker which when expressed is functional in the target cell in which the vector is used. A fourth DNA sequence encoding a negative selection marker, also functional in the target cell, is positioned 5' to the first or 3' to the second DNA sequence and is substantially incapable of homologous recombination with the target DNA sequence.

Abstract: Positive-negative selector (PNS) vectors are provided for modifying a target DNA sequence contained in the genome of a target cell capable of homologous recombination. The vector comprises a first DNA sequence which contains at least one sequence portion which is substantially homologous to a portion of a first region of a target DNA sequence. The vector also includes a second DNA sequence containing at least one sequence portion which is substantially homologous to another portion of a second region of a target DNA sequence. A third DNA sequence is positioned between the first and second DNA sequences and encodes a positive selection marker which when expressed is functional in the target cell in which the vector is used. A fourth DNA sequence encoding a negative selection marker, also functional in the target cell, is positioned 5' to the first or 3' to the second DNA sequence and is substantially incapable of homologous recombination with the target DNA sequence.

Abstract: Positive-negative selector (PNS) vectors are provided for modifying a target DNA sequence contained in the genome of a target cell capable of homologous recombination. The vector comprises a first DNA sequence which contains at least one sequence portion which is substantially homologous to a portion of a first region of a target DNA sequence. The vector also includes a second DNA sequence containing at least one sequence portion which is substantially homologous to another portion of a second region of a target DNA sequence. A third DNA sequence is positioned between the first and second DNA sequences and encodes a positive selection marker which when expressed is functional in the target cell in which the vector is used. A fourth DNA sequence encoding a negative selection marker, also functional in the target cell, is positioned 5' to the first or 3' to the second DNA sequence and is substantially incapable of homologous recombination with the target DNA sequence.

Abstract: A method of suppressing a nonsense codon in a gene in a mammalian cell by preparing an oligonucleotide primer having a mismatched anticodon region corresponding to the nonsense codon; preparing a DNA template for production of a tRNA molecule enabling the insertion of an amino acid when the nonsense codon is translated; forming a suppressor gene from said template and primer by site specific mutagenesis; and transforming the suppressor gene into the cell.