Journal ArticleDOI
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 +8 more
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TLDR
A 650 kilobase yeast artificial chromosome that contains the entire, unrearranged 400 kb human APP gene into mouse embryonic stem (ES) cells by lipid–mediated transfection and this transgenic strategy may prove invaluable for the development of mouse models for AD and DS.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.read more
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Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein.
Dora Games,David S. Adams,Ree Alessandrini,Robin Barbour,Patricia Borthelette,Catherine Blackwell,Tony Carr,J. C. Clemens,Thomas Donaldson,Frances Gillespie,Terry Guido,Stephanie Hagopian,Kelly Johnson-Wood,Karen Khan,Michael K. Lee,Paul Leibowitz,Ivan Lieberburg,Sheila P. Little,Eliezer Masliah,Lisa McConlogue,Martin Montoya-Zavala,Lennart Mucke,Lisa Paganini,Elizabeth Penniman,Michael Power,Dale Schenk,Peter Seubert,Ben W. Snyder,Ferdie Soriano,Hua Tan,James Vitale,Sam Wadsworth,Ben Wolozin,Jun Zhao +33 more
TL;DR: Transgenic mice that express high levels of human mutant APP support a primary role for APP/Aβ in the genesis of AD and could provide a preclinical model for testing therapeutic drugs.
Journal ArticleDOI
Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology
Christine Sturchler-Pierrat,Dorothee Abramowski,Mairead Duke,Karl-Heinz Wiederhold,Claudia Mistl,Sabin Rothacher,Birgit Ledermann,Kurt Bürki,Peter Frey,Paolo Paganetti,Caroline Waridel,Michael E. Calhoun,Mathias Jucker,Alphonse Probst,Matthias Staufenbiel,Bernd Sommer +15 more
TL;DR: These mice resemble major features of AD pathology and suggest a central role of A beta in the pathogenesis of the disease.
Journal ArticleDOI
Mechanisms of Neuronal Degeneration in Alzheimer's Disease
TL;DR: Although a consensus on the primary mechanism(s) of neuronal degeneration in AD has not yet been reached, several potential pathogenic mechanisms have emerged and the recent identification of new AD susceptibility genes promises to rapidly advance understanding of the primary neurodegenerative mechanisms.
Journal ArticleDOI
A mouse model for Down syndrome exhibits learning and behaviour deficits
Roger H. Reeves,N.G. Irving,Timothy H. Moran,Anny Wohn,Cheryl A. Kitt,Sangram S. Sisodia,Cecilia Schmidt,Roderick T. Bronson,Muriel T. Davisson +8 more
TL;DR: In this article, the reproducibility of this phenotype among mice with segmental trisomy 16 (Ts65Dn mice) indicates that dosage imbalance for a gene or genes in this region contributes to this impairment.
Journal ArticleDOI
β-amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity
Hui Zheng,Minghao Jiang,Myrna E. Trumbauer,Dalip J. S. Sirinathsinghji,R. Hopkins,Smith David W,Robert P. Heavens,Gerard R. Dawson,Susan Boyce,Michael W. Conner,Karla Stevens,Hilda H. Slunt,Sangram S. Sisodia,Howard Y. Chen,Lex H.T. Van der Ploeg +14 more
TL;DR: To understand the in vivo function of APP and its processing, an APP-null mutation is generated in mice and it is shown that the APP-deficient mice exhibited a decreased locomotor activity and forelimb grip strength, indicating a compromised neuronal or muscular function.
References
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Journal ArticleDOI
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity
TL;DR: A technique for conveniently radiolabeling DNA restriction endonuclease fragments to high specific activity is described, and these "oligolabeled" DNA fragments serve as efficient probes in filter hybridization experiments.
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity
TL;DR: In this article, a technique for conveniently radiolabeling DNA restriction endonuclease fragments to high specific activity is described, where DNA fragments are purified from agarose gels directly by ethanol precipitation and are then denatured and labeled with the large fragment of DNA polymerase I, using random oligonucleotides as primers.
Journal ArticleDOI
A simple salting out procedure for extracting DNA from human nucleated cells
TL;DR: A rapid, safe and inexpensive method was developed to simplify the deprotein-ization procedure that yielded quantities comparable to those obtained from phenol-chloroform extractions, rendering the entire process of RFLP analysis free of toxic materials.
Journal ArticleDOI
Transformation of intact yeast cells treated with alkali cations.
TL;DR: The transformation efficiency with Cs+ or Li+ was comparable with that of conventional protoplast methods for a plasmid containing ars1, although not for plasmids containing a 2 microns origin replication.
Journal ArticleDOI
Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein
George G. Glenner,Caine W. Wong +1 more
TL;DR: A purified protein derived from the twisted beta-pleated sheet fibrils in cerebrovascular amyloidosis associated with Alzheimer's disease has been isolated and Amino acid sequence analysis and a computer search reveals this protein to have no homology with any protein sequenced thus far.
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