Expression of APP in transgenic mice: a comparison of neuron-specific promoters.
The beta-amyloid precursor protein (APP) carries mutations in codons 717 or 670/671, which cosegregate with familial forms of Alzheimer's disease (AD). As an initial step to study the related pathogenetic mechanisms in vivo we have generated transgenic mice expressing APP with these mutations. Several neuron-specific promoters were used to drive expression of human APP cDNAs. Only the Thy-1 promoter yielded transgene expression levels comparable to or above the endogenous mouse levels. Deletion of a 121 bp sequence from the 3' untranslated region of APP appeared to increase mRNA levels. Transgene mRNA was found throughout the brain with highest levels in hippocampus and cerebral cortex. Accordingly, human APP was detected in these regions by Western blotting. Protein levels paralleled mRNA levels reaching or exceeding the amount of endogenous APP. Variable reactivity of human APP in cell bodies was shown by immunocytochemistry. Although our initial histological examinations did not reveal any alterations characteristic of AD, further studied will be required.
Andrä
K
K
Preclinical Research, Sandoz Pharma Ltd, Basel, Switzerland.
Abramowski
D
D
Duke
M
M
Probst
A
A
Wiederhold
K H
KH
Bürki
K
K
Goedert
M
M
Sommer
B
B
Staufenbiel
M
M
D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D060588:LIM Domain Proteins; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D010751:Phosphopyruvate Hydratase / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors / Q000494:pharmacology
D016564:Amyloid beta-Protein Precursor; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C065072:LMO1 protein, human; C513044:Lmo1 protein, mouse; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D010751:Phosphopyruvate Hydratase