Multicellular living organisms and unmodified parts thereof and – Nonhuman animal – Transgenic nonhuman animal
Reexamination Certificate
2006-06-13
2006-06-13
Crouch, Deborah (Department: 1632)
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
Transgenic nonhuman animal
C800S003000, C800S012000
Reexamination Certificate
active
07060870
ABSTRACT:
The present invention provides for a transgenic non-human animal whose cells contain a DNA sequence comprising: (a) a nerve tissue specific promoter operatively linked to a DNA sequence which encodes amyloid-beta peptide alcohol dehydrogenase (ABAD), and (b) a nerve tissue specific promoter operatively linked to a DNA sequence encoding a mutant human amyloid precursor protein hAPP695, hAPP751 and hAPP770 bearing mutations linked to familial Alzheimer's disease in humans, wherein the non-human animal exhibits at least one phenotype from the group consisting of: reduced basal synaptic transmission; inhibited synaptic plasticity; increased neuronal stress; elevated 4-hydroxynonenal in cerebral cortex; increased heme oxygenase type I in cerebral cortex; decreased synaptophysin in cerebral cortex; decreased micortubule-associated protein 2 in cerebral cortex; and increased levels of activated caspase 3 antigen in cortical neurons.
REFERENCES:
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He X-Y, Schulz H, Yang S-Y: A human brain L-3-hydroxyacyl coenzyme A dehydrogenase is identical to amyloid beta-peptide-binding protein involved in Alzheimer's disease.J Biol Chem1998; 273: 10741-10746 (Exhibit 2).
Lipton P (1999)Physiol. Rev.79: 1431-1568 (Exhibit 3).
White A, Zheng H, Galatis D, Maher F, Hesse L, Multhaup G, Beyreuther K, Masters C, Cappai R: Survival of cultured neurons from amyloid precursor protein knock-out mice against Alzheimer's amyloid-β toxicity and oxidative stress.J Neurosci1998; 18: 6207-6217 (Exhibit 4).
Yan SD, Fu J, Soto C, Chen X, Zhu H, Al-Mohanna F, Collison K, Zhu A, Stern E, Saido T, Tohyama M, Ogawa S, Roher A, Stern D: An intracellular protein that bind amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease.Nature(Lond) 1997; 389:689-695 (Exhibit 5).
Yan SD, Shi Y, Zhu A, Fu J, Zhu H, Zhu Y, Gibson L, Collison K, Al-Mohanna F, Ogawa S, Roher A, Clarke S, Stern DM: Role of ERAB/L-3-hydroxyacycl-Coenzyme A dehydrogenase type II activity in amyloid beta-peptide-induced cytotoxicity.J Biol Chem1998; 274:2145-2156 (Exhibit 6).
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Stern David M.
Yan Shi Du
Cooper & Dunham LLP
Crouch Deborah
The Trustees of Columbia University in the City of New York
White John P.
LandOfFree
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