Appeal No. 2003-0835 Page 3
Application No. 09/419,371
The present invention is based on Applicants’ discovery of
the dCREB1 and dCREB2 genes. The present invention is further
based on Applicants’ discovery that the Drosophila CREB2 gene
codes for proteins of opposite functions. One isoform (e.g.,
dCEB2-a) encodes a cyclic 3', 5'-adenosine monophosphate
(cAMP)-responsive transcriptional activator. Another isoform (e.g.,
dCREB2-b) codes for an antagonist which blocks the activity of the
activator.
When the blocking form is placed under the control of the
heat-shock promoter, and transgenic flies are made, a brief shift in
temperature induces the synthesis of the blocker in the transgenic
fly. This induction of the blocker (also referred to herein as the
repressor) specifically disrupts long-term, protein synthesis
dependent memory of an odor-avoidance behavioral paradigm.
Specification, page 2.
The specification teaches further that:
A further embodiment of the invention relates to an assay of
pharmaceutical agents for their property as facilitators or hinderers
of long term memory in animals. The assay is performed by
administering the pharmaceutical agent to Drosophila prior to
subjecting the Drosophila to a Pavlovian olfactory learning regimen.
This regimen assesses the long term memory capabilities of the
Drosophila by subjecting the flies to a massed and/or spaced
training schedule. Transgenic lines of these flies containing altered
dCREB2 genes can be used to further elucidate the long term
memory facilitation or hindering property of the pharmaceutical
agent. The assay provides data regarding the acquisition of long
term memory by the Drosophila after exposure to the
pharmaceutical agent. These data are compared to long term
memory acquisition data from Drosophila that have not been
exposed to the pharmaceutical agent. If the exposed flies display
faster or better retained long term memory acquisition than the
unexposed flies, the pharmaceutical agent can be considered a
facilitator of long term memory. Conversely, if the exposed flies
display slower or less retained long term memory acquisition than
the unexposed flies, the pharmaceutical agent can be considered a
hinderer of long term memory. Since the genetic locus for this long
term memory assay in Drosophila resides in the dCREB2 gene, the
results from this assay can be directly applied to other animals that
have homologous genetic loci (CREB2 or CREM genes).
Id. at 6.
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