Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice [corrected].
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.
Lamb
B T
BT
Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Sisodia
S S
SS
Lawler
A M
AM
Slunt
H H
HH
Kitt
C A
CA
Kearns
W G
WG
Pearson
P L
PL
Price
D L
DL
Gearhart
J D
JD
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D018244:Chromosomes, Artificial, Yeast; D005786:Gene Expression Regulation; D005796:Genes; D015894:Genome, Human; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis*; D013234:Stem Cells
D016564:Amyloid beta-Protein Precursor; D011993:Recombinant Fusion Proteins