Abstract: The subject invention provides a selectively cleavable probe comprising an F(ab) fragment linked to one or more labels by a chemically cleavable disulfide bond. The subject invention also provides a process of immunostaining a sample comprising staining the sample with a selectively cleavable probe. The subject invention further provides a process of immunostaining a sample comprising (a) obtaining a probe comprising a primary antibody against a preselected target linked to biotin, (b) staining the sample with the probe of step (a), and (c) staining the sample with a selectively cleavable probe, wherein the F(ab) fragment is an anti-biotin F(ab) fragment.

Abstract: 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.

Abstract: 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.

Abstract: The present invention provides for a method of evaluating whether a compound is effective in activating a calcium-calmodulin dependent kinase II? 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? 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? promoter.

Abstract: The present invention provides for a method of evaluating whether a compound is effective in activating a calcium-calmodulin dependent kinase II? 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? 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? promoter.

Abstract: The present invention provides for a recombinant nucleic acid molecule comprising a region of a calcium-calmodulin dependent kinase II? promoter operatively linked to a gene of interest. The region of a calcium-calmodulin dependent kinase II? promoter may comprise an 8.5 kilobase nucleic acid sequence which corresponds to the nucleic acid sequence of ATCC Accession No.: ______, designated pMM281. The present invention also provides a human cell line 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? promoter region which has a nucleotide sequence corresponding to the sequence of ATCC Accession No. ______, designated pMM281. The present invention also provides for a transgenic nonhuman mammal whose germ or somatic cells contain a nucleic acid molecule which encodes a gene of interest under the control of a CaMKII? promoter (ATCC Accession No.

Abstract: 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? 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° C. in 0.2× standard sodium citrate buffer is also provided.

Abstract: 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.

Abstract: 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.

Abstract: The present invention provides for a recombinant nucleic acid molecule comprising a region of a calcium-calmodulin dependent kinase II&agr; promoter operatively linked to a gene of interest. The region of a calcium-calmodulin dependent kinase II&agr; promoter may comprise an 8.5 kilobase nucleic acid sequence which corresponds to the nucleic acid sequence of ATCC Accession No. ______, designated pMM281. The present invention also provides a human cell line 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&agr; promoter region which has a nucleotide sequence corresponding to the sequence of ATCC Accession No. ______, designated pMM281. The present invention also provides for a transgenic nonhuman mammal whose germ or somatic cells contain a nucleic acid molecule which encodes a gene of interest under the control of a CaMKII&agr; promoter (ATCC Accession No.

Abstract: The present invention provides for a transgenic nonhuman mammal whose germ or somatic cells contain a nucleic acid molecule which encodes calcineurin or a variant thereof under the control of a regulatable promoter, introduced into the mammal, or an ancestor thereof, at an embryonic stage. The present invention also provides for a method of evaluating whether a compound is effective in improving long-term memory in a subject suffering from impaired long-term memory which comprises: (a) administering the compound to the transgenic nonhuman mammal of claim 1 wherein the mammal has increased brain-specific calcineurin activity due to expression of the nucleic acid, and (b) comparing the long-term memory of the mammal in step (a) with the long-term memory of the mammal in the absence of the compound so as to determine whether the compound is effective in rescuing the long-term memory defect in the subject.

Abstract: 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.

Abstract: 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.

Abstract: The present invention provides for a recombinant DNA construct for expressing a gene of interest comprising a mouse calcium-calmodulin-dependent kinase IIá 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.

Abstract: The present invention provides a transgenic nonhuman mammal and mammalian cells whose genomes encode a calcineurin inhibitor. The expression of the inhibitor is targeted to the forebrain and may be induced experimentally. The present invention further provides a composition of matter comprising the nucleic acid sequences encoding the inhibitor and additional sequences required for its targeted expression and regulation. In addition, the present invention provides methods for determining whether an agent inhibits long-term potentiation and/or learning and memory in a mammal.

Abstract: The present invention provides for a transgenic nonhuman mammal whose germ or somatic cells contain a nucleic acid molecule which encodes calcineurin or a variant thereof under the control of a regulatable promoter, introduced into the mammal, or an ancestor thereof, at an embryonic stage. The present invention also provides for a method of evaluating whether a compound is effective in improving long-term memory in a subject suffering from impaired long-term memory which comprises: (a) administering the compound to the transgenic nonhuman mammal of claim 1 wherein the mammal has increased brain-specific calcineurin activity due to expression of the nucleic acid, and (b) comparing the long-term memory of the mammal in step (a) with the long-term memory of the mammal in the absence of the compound so as to determine whether the compound is effective in rescuing the long-term memory defect in the subject.

Abstract: The present invention provides for a recombinant nucleic acid molecule comprising a region of a calcium-calmodulin dependent kinase II&agr; promoter operatively linked to a gene of interest. The region of a calcium-calmodulin dependent kinase II&agr; promoter may comprise an 8.5 kilobase nucleic acid sequence which corresponds to the nucleic acid sequence of ATCC Accession No. ______ , designated pMM281. The present invention also provides a human cell line 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&agr; promoter region which has a nucleotide sequence corresponding to the sequence of ATCC Accession No. ______ designated pMM281. The present invention also provides for a transgenic nonhuman mammal whose germ or somatic cells contain a nucleic acid molecule which encodes a gene of interest under the control of a CaMKII&agr; promoter (ATCC Accession No.

Abstract: 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.