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

Bruce T. Lamb, Sangram S. Sisodia, Ann M. Lawler, Hilda H. Slunt, Cheryl A. Kitt, William G. Kearns, Peter L. Pearson, Donald L. Price, John D. Gearhart

Research output: Contribution to journalArticle

266 Scopus citations

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)22-30
Number of pages9
JournalNature genetics
Volume5
Issue number1
DOIs
StatePublished - Sep 1993

ASJC Scopus subject areas

  • Genetics

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    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. (1993). Introduction and expression of the 400 kilobase precursor amyloid protein gene in transgenic mice. Nature genetics, 5(1), 22-30. https://doi.org/10.1038/ng0993-22