Expression of human FE65 in amyloid precursor protein transgenic mice is associated with a reduction in beta-amyloid load.

FE65 is an adaptor protein that interacts with the cytoplasmic tail of the amyloid precursor protein (APP). In cultured non-neuronal cells, the formation of the FE65-APP complex is a key element for the modulation of APP processing, signalling and beta-amyloid (Abeta) production. The functions of FE65 in vivo, including its role in the metabolism of neuronal APP, remain to be investigated.

Akt3 overexpression in the heart results in progression from adaptive to maladaptive hypertrophy.

Akt is a serine/threonine kinase that mediates a variety of cellular responses to external stimuli. Among the three members of mammalian Akt (Akt1, Akt2 and Akt3), Akt3 is unique in that it has an alternatively spliced variant that lacks the carboxy-terminal regulatory phosphorylation site. However, little is known regarding in vivo functions of Akt3 and its spliced variant.

Massive CA1/2 neuronal loss with intraneuronal and N-terminal truncated Abeta42 accumulation in a novel Alzheimer transgenic model.

Alzheimer's disease (AD) is characterized by a substantial degeneration of pyramidal neurons and the appearance of neuritic plaques and neurofibrillary tangles. Here we present a novel transgenic mouse model, APP(SL)PS1KI that closely mimics the development of AD-related neuropathological features including a significant hippocampal neuronal loss. This transgenic mouse model carries M233T/L235P knocked-in mutations in presenilin-1 and overexpresses mutated human beta-amyloid (Abeta) precursor protein.

Robust functional gene validation by adenoviral vectors: one-step Escherichia coli-derived recombinant adenoviral genome construction.

We describe here a clonal approach for efficient and robust construction of recombinant adenoviral genomes that holds certain advantages over existing approaches. Transgenes of interest are cloned into a small, conditionally replicating plasmid containing the left end of a recombinant adenoviral genome, encompassing pIX coding regions. Transformation of this plasmid into recombination-competent Escherichia coli bearing a plasmid containing the right end of a recombinant adenoviral genome, commencing from pIX coding regions, yields a stable co-integrated plasmid encoding a full adenoviral genome, by virtue of shared homology in pIX coding regions contained in both plasmids.

Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer's disease.

According to the "amyloid hypothesis of Alzheimer's disease," beta-amyloid is the primary driving force in Alzheimer's disease pathogenesis. Despite the development of many transgenic mouse lines developing abundant beta-amyloid-containing plaques in the brain, the actual link between amyloid plaques and neuron loss has not been clearly established, as reports on neuron loss in these models have remained controversial. We investigated transgenic mice expressing human mutant amyloid precursor protein APP751 (KM670/671NL and V717I) and human mutant presenilin-1 (PS-1 M146L).