Introduction and expression of the 400 kilobase precursor amyloid protein gene in transgenic mice

@article{Lamb1993IntroductionAE,
  title={Introduction and expression of the 400 kilobase precursor amyloid protein gene in transgenic mice},
  author={Bruce T. Lamb and Sangram S. Sisodia and Ann M. Lawler and Hilda H. Slunt and Cheryl A. Kitt and William G. Kearns and Peter L Pearson and Donald L. Price and John D. Gearhart},
  journal={Nature Genetics},
  year={1993},
  volume={5},
  pages={22-30}
}
Overexpression of the gene encoding the β–amyloid precursor protein (APP) may have a key role in the pathogenesis of both Alzheimer's disease (AD) and Down Syndrome (DS). We have therefore introduced a 650 kilobase (kb) yeast artificial chromosome (YAC) that contains the entire, unrearranged 400 kb human APP gene into mouse embryonic stem (ES) cells by lipid–mediated transfection. ES lines were generated that contain a stably integrated, unrearranged human APP gene. Moreover, we demonstrate… 
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296 Citations

Alzheimer's disease and transgenic mice.
TLDR
Although transgenic mice can demonstrate expression of transgenic APP in several tissues including brain, expression levels never exceeded those of the endogenous mouse APP, the question remains open whether overexpression of APP is sufficient to induce Alzheimer pathology.
Amyloid production and deposition in mutant amyloid precursor protein and presenilin-1 yeast artificial chromosome transgenic mice
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It is document that a mutant APP YAC transgenic mouse develops Aβ deposits and that this deposition is accelerated when the animals are mated to homozygosity and/or to mutant PS-1 YACtransgenic mice.
The coding sequence of amyloid-β precursor protein APP contains a neural-specific promoter element
Amyloid precursor protein increases cortical neuron size in transgenic mice
Mice transgenic for a human amyloid precursor protein promoter-lacZ reporter construct
TLDR
It is concluded that the 2-kb region upstream of the APP transcription initiation site contains some elements responsible for the tissue-specific expression of this gene, but does not contain all the cis-acting elements sufficient for either the differential tissue distribution ofThis gene or the regulation of this genes subsequent to neural damage.
Rational design of an animal model for alzheimer's disease: introduction of multiple human genomic transgenes to reproduce AD pathology in a rodent
Accumulation of β-Amyloid fibrils in pancreas of transgenic mice
Enhanced Amyloidogenic Processing of the β-Amyloid Precursor Protein in Gene-targeted Mice Bearing the Swedish Familial Alzheimer's Disease Mutations and a “Humanized” Aβ Sequence*
TLDR
The neuropathological consequences of human Aβ overproduction can be evaluated longitudinally in the absence of potential mitigating effects of APP overexpression or presence of the mouse Aβ peptide.
Transgenic mice expressing the amyloid β protein-containing carboxyl-terminal fragment of the Alzheimer amyloid precursor protein
TLDR
The results suggest that the expression of the Aβ containing carboxyl-terminal fragment itself may not directly lead to AD-like neuropathologic changes in vivo.
Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology.
TLDR
These mice resemble major features of AD pathology and suggest a central role of A beta in the pathogenesis of the disease.
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