Transgenic mice expressing APP-Swedish mutation develop progress

Details Transgenic mice expressing APP-Swedish mutation develop progress Transgenic mice expressing APP-Swedish mutation develop progress

1996-06-17

1999-03-02

Crouch, Deborah

Multicellular living organisms and unmodified parts thereof and

Nonhuman animal

800DIG1, 424 92, 935 60, C12N 500, C12N 1500, A61K 4900

Patent

active

058773991

ABSTRACT:
Provided is a transgenic non-human eukaryotic animal whose germ cells and somatic cells contain the amyloid precursor protein sequence introduced into the animal, or an ancestor of the animal, at an embryonic stage. In mice, an age-related CNS disorder characterized by agitation, neophobia, seizures, inactivity, diminished cerebral glucose utilization, cortico-limbic gliosis, and death, develops. An acceleration of this disorder occurs in transgenic mice expressing human and mouse Alzheimer amyloid precursor proteins (APP) produced using a hamster prion protein gene-derived cosmid vector that confers position-independent, copy number-dependent expression. In transgenic mice the disorder develops in direct relationship to brain levels of transgenic APP, but mutant APP confers the phenotype at lower levels of expression than wild-type APP. The disorder occurs in the absence of extracellular amyloid deposition, indicating that some pathogenic activities of APP are dissociated from amyloid formation.

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