Expression of the human beta-amyloid precursor protein gene from a yeast artificial chromosome in transgenic mice.

One hallmark of Alzheimer disease is the formation in the brain of amyloid plaques containing a small peptide derived from the beta-amyloid precursor protein (APP). The APP gene exhibits a complex pattern of expression in peripheral tissues and in the brain. The entire human APP gene was introduced into embryonic stem (ES) cells by co-lipofection of a 650-kb yeast artificial chromosome (YAC). Three ES lines containing an essentially intact YAC were isolated, and expression of human APP mRNAs at levels comparable to those of endogenous mouse APP transcripts was obtained. A transgenic mouse line was established by germ-line transmission of the APP YAC. RNase protection analysis of human APP mRNAs demonstrated appropriate splicing of the primary APP transcript in ES cells and in the brain of a transgenic animal. These mice may be useful for elucidating the function of the various APP isoforms in vivo.