Introduction and expression of the 400 kilobase precursor amyloid protein gene in transgenic mice
Abstract
Overexpression of the gene encoding the beta-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 germ line transmission of the APP YAC in transgenic mice and expression of human APP mRNA and protein at levels comparable to endogenous APP. This transgenic strategy may prove invaluable for the development of mouse models for AD and DS.
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The R1.40 model exhibits gradual deposition of primarily Aβ40.
“we mated Cx3cr1 knockout mice to two different mouse models of AD that exhibit either rapid deposition of primarily A42 (the APPPS1 model) 21 or gradual deposition of primarily A40 (the R1.40 model).[22][23][24]”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [22]
The R1.40 transgene is a full genomic copy of human APP carrying the K670M/N671L mutation.
“The R1.40 transgene is a full genomic copy of human APP (carried on a 650-kb yeast artificial chromosome clone) carrying the K670M/N671L familial AD mutation associated with early-onset familial AD.”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [22]
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References 69 · Cited by 311
- Authors
- Lamb, B. T., Sisodia, S. S., Lawler, A. M., Slunt, H. H., Kitt, C. A., Kearns, W. G., Pearson, P. L., Price, D. L., & Gearhart, J. D.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Nature Genetics
- Published
- 1993-09-01
- Volume
- 5
- Issue
- 1
- Pages
- 22-30
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2023511811
- Cited by
- 311
- References
- 69
- Citations by year
- 2026: 3 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 9 · 2016: 5 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 12
- FWCI
- 15.99
- Type
- journal article
- Language
- en
- Update notices
- correction (1993-11-01)
- Open access
- closed
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Keywords
- amyloid precursor protein, APP gene, transgenic mice, yeast artificial chromosomes, mouse embryonic stem cells, germline transmission, Alzheimer's disease, Down syndrome, mouse model, gene overexpression
- MeSH terms
- Animals, Base Sequence, Gene Expression Regulation, Genes, Humans, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Organ Specificity, Recombinant Fusion Proteins, Stem Cells, Genome, Human, Polymerase Chain Reaction, Amyloid beta-Protein Precursor, Chromosomes, Artificial, Yeast, Mice
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