Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of... – Rodent cell – per se
Reexamination Certificate
1997-11-12
2003-01-21
Baker, Anne-Marie (Department: 1632)
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
Rodent cell, per se
C435S325000, C435S352000, C536S023100, C536S023500, C536S024100
Reexamination Certificate
active
06509190
ABSTRACT:
BACKGROUND OF THE INVENTION
Throughout this application, various publications are referenced by author and date. Full citations for these publications may be found listed alphabetically at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
The insight that memory has time-dependent phases dates to 1890 when William James first proposed a distinction between a primary or short-term memory, a memory that has to be maintained continuously in consciousness, and secondary or long-term memory that can be dropped from consciousness and could be recalled at will at a later time (James, 1890). According to James view, short-term memory holds information for a few seconds whereas long-term memory holds information for long periods of time. Subsequent experimental work suggested that these two phases of memory are usually in series and that the transition from short- to long-term memory is facilitated by an increase in the saliency or the number of training trials (Ebbinghaus, 1885; Weiskrantz, 1970; Craik and Lockhart, 1972; Wickelgren, 1983; Mandel et al., 1989).
The distinction between these two major phases was placed on a firmer biochemical basis when long-term memory was found to require the synthesis of new proteins, whereas short-term memory does not (Davis and Squire, 1984). These Biochemical studies also revealed that short-term memory often lasted many minutes, and therefore was more enduring than the primary memory delineated y James. These studies therefore suggested that short-term memory may in turn have subdivisions, and that in addition to primary or working memory, there is a subsequent intermediate stage of, protein synthesis-independent, short-term memory. Further support for subcomponents of memory have also emerged from genetic studies in Drosophila and pharmacological studies in rodents and chicks (McGaugh, 1968; Cherkin, 1969; Gibbs and Ng, 1977; Frieder and Allweis, 1982; Rosenzweig et al., 1993; Tully et al., 1994; Zhao et al., 1995 a and b; Bennet et al., 1996).
In addition to being able to distinguish temporal phases in memory storage, studies in human and monkey also delineated two distinct neural systems for long-term memory based upon the types of information stored. Bilateral lesions of the medial temporal lobe revealed an impairment in declarative long-term memory, a memory for people, places and objects but these lesions spared non-declarative memory for perceptual and motor skill. Particularly, interesting was the finding that the lesions of the medial temporal lobe system, that interfere with declarative memory, only interfere with the long-term form of this memory and not with components of short-term memory, in particular not with working memory (Scoville and Milner, 1957; Mishkin, 1978; Zola-Morgan and Squire, 1985; Squire, 1987; Overman et al., 1990; Alvarez et al., 1994). These results indicate that structures in the medial temporal lobe, in particular the hippocampus, specifically subserve long-term memory but not some components of short-term memory.
SUMMARY OF THE INVENTION
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. 98582, designated pMM403. 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, introduced into the mammal, or an ancestor therefore, at an embryonic stage. Another embodiment or the present invention is a method of evaluating whether a compound is effective in treating symptoms of a neurological disorder in a subject which comprises: (a) administering the compound to the 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, and (b) comparing the neurological function the mammal in step (a) with neurological function of the transgenic mammal in the absence of the compound, thereby determining whether the compound is effective in treating symptoms of the neurological disorder in a subject.
REFERENCES:
Chen et al. Retinoic acid stimulates a-CaMKII gene expression in PC12 cells at a distinct transcription initiation site. J. Neurosci. 16(18): 5704-5714, Sep. 1996.*
Lehninger, AL Biochemistry. (Worth Publishers, Inc., New York, 2nd ed.) p. 717, 1975.*
Olson et al. Functional identification of the promoter for the gene encoding the alpha subunit of calcium/calmodulin-dependent protein kinase II. Proc. Natl. Acad. Sci. USA 92: 1659-1663, Feb. 1995.*
Sunyer et al. Sequence analysis and DNA-protein interactions within the 5′ flanking region of the Ca2+/calmodulin-dependent protein kinase II alpha-subunit gene. Proc. Natl. Acad. Sci. USA 87: 278-282, Jan. 1990.*
International Search Report issued Feb. 24, 2000 in connection with corresponding International Application No. PCT/US98/24157.
Chen et al. Retinoic acid stimulates alpha-CaMKII gene expression in PC12 cells at a distinct transcription initiation site. J. of Neuroscience, Sep. 15, 1996, vol. 16, No. 18, pp. 5704-5714.
Winder et al. Genetic and Pharmacological evidence for a novel, intermediate phase of long-term potentiation suppressed by calcineurin. Cell. Jan. 9, 1998, vol. 92, pp. 25-37.
Chen, J. And Kelly P.T.(1996) Retinoic Acid Stimulates &agr;-CAMKII Gene Expression in PC12 Cells at a Distinct Transcription Initiation Site.J. of Neuroscience16(18): 5704-5714.
Kojima, N,et al., (1997), Rescuing Impairment of Long-Term Potentiation in Fyn-Deficient Mice By Introducing Fyn Transgene.Proc. Natl. Acad. Sci.94: 4761-4765.
Olson, N.J. et al., (1995), Functional Identification Of The Promoter For The Gene Encoding The &agr;Subunit of Calcium/Calmodulin-Dependent Protein Kinase II.Proc. Natl. Acad. Sci.92: 1659-1663.
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McHugh, Thomas J. et al., (1996) Cell 87: 1339-1349.
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Tsien, Joe Z. et al., (1996) Cell 87: 1317-1326.
Bach, M.E. et al., (1995) Cell 81: 905-915.
Sunyer et al, “Sequence Analysis and DNA-Protein Interaction Within the 5′ Flanking Region of the Calcium Ion Alpha-Subunit Gene”Proc. Natl. Acad. Sci. U.S.A.,87:278-282 (1990).
Kandel Eric R.
Mayford Mark
Baker Anne-Marie
Cooper & Dunham LLP
The Trustees of Columbia University in the City of New York
White John P.
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