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

Nature Genetics volume 5, pages 22–30 (1993)Cite this article

A Correction to this article was published on 01 November 1993

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.

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Authors and Affiliations

  1. Developmental Genetics Laboratory, Departments of Gynecology and Obstetrics and Physiology, 205 Physiology Building, 725 N. Wolfe Street, USA

    Bruce T. Lamb, Ann M. Lawler & John D. Gearhart

  2. Department of Pathology, Neuropathology Laboratory, 558 Ross Building, 720 Rutland Avenue, USA

    Sangram S. Sisodia, Hilda H. Slunt & Cheryl A. Kitt

  3. Center for Medical Genetics, Department of Medicine, 347 Ross Building, The John Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, Maryland, 21205, USA

    William G. Kearns, Peter L. Pearson & Donald L. Price

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Lamb, B., Sisodia, S., Lawler, A. et al. Introduction and expression of the 400 kilobase precursor amyloid protein gene in transgenic mice. Nat Genet 5, 22–30 (1993). https://doi.org/10.1038/ng0993-22

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