Höfling C, Morawski M, Zeitschel U, Zanier ER, Moschke K, Serdaroglu A, Canneva F, von Hörsten S, De Simoni MG, Forloni G, Jäger C, Kremmer E, Roßner S, Lichtenthaler SF, Kuhn PH. Differential transgene expression patterns in Alzheimer mouse models revealed by novel human amyloid precursor protein-specific antibodies. Aging Cell. 2016 Oct;15(5):953-63. Epub 2016 Jul 29 PubMed.

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  1. This paper very nicely demonstrates that the use of different heterologous promoters to drive various APP cDNAs produces distinct expression patters. This finding is less surprising than cautionary, and points to the need to invest in the development of novel mouse models, with targeted replacement of relevant murine genes by their human counterparts. Not only should specific exons within genes be replaced, but the entire gene, replete with all its regulatory regions, must be carefully excised and the entire human counterpart inserted in its place. Since it is likely that abnormal phenotypes will not arise unless the human genes are over-expressed, the promoter regions may need to be precision-engineered to allow for regulation of expression levels. The technology to accomplish this work exists today but did not, for instance, when I made Tg2576 more than 20 years ago. Unfortunately, we lack funding for such endeavors now. In the meantime, the AD field is, in my opinion, held back by the possibility that the phenotypes in the available mice are not ones that are most relevant to the human disease.

    View all comments by Karen Hsiao Ashe

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  1. New APP Antibodies Expose Variation in Mouse Models of AD