Columbia University

Eric R Kandel

Mark Mayford

Dusan Bartsch

Gareth Tibbs

Seth Grant

Steven Siegelbaum

Bina Santoro

Scott A Small

Ilias Pavlopoulos

Mary E Bach

Kausik Si

Mirella Ghirardi

Min Zhuo

Described is a transgenic mouse with two transgenes, each of which transgene comprises a DNA sequence encoding a dominant negative form of RbAp48 protein, wherein the expression of the dominant negative form of RbAp48 is spatially restricted to the forebrain by a CaM Kinase IIa promoter and wherein the expression of the dominant negative form of RbAp48 is controlled by tetracycline-controlled transcriptional activation. Also provided are methods for evaluating in the transgenic mouse the potential therapeutic effect of an agent for slowing, inhibiting or preventing age-related memory decline in a mammalian subject.

RbAp48 transgenic mice for drug discovery in age-related memory decline

The present invention provides methods for determining whether an agent facilitates the conversion of a cytoplasmic polyadenylation element binding (CPEB) protein from its non-prion form to its prion form. This invention also provides methods for determining the presence and amount of the prion form of CPEB protein in a cell. This invention also provides methods for facilitating the conversion of a non-prion CPEB protein to its prion form. This invention also provides an isolated prion form cytoplasmic polyadenylation element binding (CPEB) protein and compositions comprising a therapeutically effective amount of an agent that facilitates the conversion of CPEB protein from its non-prion form to its prion form, and methods of making such compositions.

Prion-like form of CPEB and related compositions and methods

The present invention provides for a method of evaluating whether a compound is effective in activating a calcium-calmodulin dependent kinase II&#x3b1; promoter in a human neuronal cell which comprises: (a) contacting the human neuronal cell which has been stably transformed by a recombinant nucleic acid molecule comprising a gene of interest operatively linked to a nucleic acid encoding a calcium-calmodulin dependent kinase II&#x3b1; promoter which has a nucleotide sequence of the promoter in ATCC Accession No. 98582 with the compound, and (b) comparing the expression level of the gene of interest in the neuronal cell in step (a) with the level in the neuronal cell in the absence of the compound, thereby determining whether the compound is effective in activating the calcium-calmodulin dependent kinase II&#x3b1; promoter.

DNA regulatory element for the expression of transgenes in neurons of a subject and uses thereof

A recombinant nucleic acid comprising nucleotides corresponding to a 3.2 kb 3' untranslated region present in mouse calcium calmodulin kinase II alpha subunit-encoding mRNA is provided. An isolated nucleic acid which hybridizes to the 3&#x2032; untranslated region of mouse calcium calmodulin kinase II alpha subunit-encoding mRNA under conditions comprising two post-hybridization washes of 15 minutes each at 42&#xb0; C. in 0.2&#xd7; standard sodium citrate buffer is also provided.

Methods and reagents for dendritic localization of polynucleotides

The present invention provides for a method to enhance long-term memory in a subject whose cAMP-responsive gene expression is repressed due to binding of a cAMP-response-element-binding-protein-2 to a protein or a DNA associated with cAMP-responsive gene expression, or both, which comprises administering to the subject a compound capable of interfering with such binding in an amount effective to interfere with binding of the protein or the DNA so as to thereby derepress cAMP-responsive gene expression in the subject and enhance the subject's long-term memory.

Method for enhancing long-term memory in a subject and uses thereof

The present invention provides an isolated nucleic acid encoding a BCNG protein or a portion thereof or BCNG-related protein or a portion thereof. The present invention further provides a method for identifying a nucleic acid in a sample which encodes a BCNG protein or a BCNG-related protein. The present invention also provides a method for testing whether a compound affects the expression of a BCNG protein or a BCNG-related protein. In addition, the present invention further provides a method for identifying a compound capable of interacting with a BCNG protein or a BCNG-related protein. Also, the present invention provides a method for identifing a compound capable of modulating BCNG protein or BCNG-related protein activity. Further, the present invention also provides a method of treating a condition in a subject which comprises administering to the subject an amount of the provided compound, effective to treat the condition.

Brain and heart cyclic nucleotide gated ion channel compounds and uses thereof

The present invention provides an isolated nucleic acid molecule encoding a brain cyclic nucleotide gated ion channel (BCNG) protein. An isolated BCNG protein is also provided as is a composition comprising a BCNG encoding nucleic acid or protein or a portion thereof. The present invention also provides a method of identifying an ion channel subunit related protein encoding nucleic acid molecule in a sample. The invention further provides a method for evaluating the ability of a compound to modulate an ion channel associated neurological, cardia, or renal condition. The invention also provides a method for evaluating the ability of a compound to interact with a BCNG-related ion channel subunit protein. Additionally, the present invention provides a method for identifying a compound capable of modulating the activity of a BCNG-related protein. The present invention additionally provides a method of treating a cardiac, renal or neurological condition. Finally, the present invention provides an antibody which specifically reacts with BCNG protein.

Brain cyclic nucleotide gated ion channel and uses thereof

The present invention provides for a recombinant DNA construct for expressing a gene of interest comprising a mouse calcium-calmodulin-dependent kinase II&aacute; promoter operatively linked to a gene of interest. The present invention also provides for a murine neuronal cell line which has been stably transformed with the recombinant DNA construct.

DNA regulatory element for the expression of transgenes in neurons of the mouse forebrain

The present invention provides a method to determine the extent of neuronal degradation due to aging, a learning disability, or a neurological disorder, which includes: (a) stimulating a neuronal cell population under suitable conditions so as to induce a late-phase long term potentiation; (b) stimulating a normal neuronal cell population under suitable conditions so as to induce a late-phase long term potentiation; and (c) comparing the duration of the late-phase long term potentiation of the neuronal cell population in step (a) with that of the normal neuronal cell population of step (b) so as to determine the extent of neuronal degradation due to aging, the learning disability or the neurological disorder. The learning disability or neurological disorder may be Alzheimer's Disease, a degenerative disorder associated with learning, memory or cognitive dysfunction, cerebral senility, multi-infarct dementia and senile dementia, electric shock induced amnesia or amnesia.

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Riverdale, NY, United States of America

Eric R Kandel