Changes in presenilin 2-binding Wnt proteins, behavior, amyloid-beta 42, gamma-secretase activity, and testosterone sensitivity in transgenic mice coexpressing tetracycline-controlled transactivator and human mutant presenilin 2
| Autor: | Jung S. Cho, Dae Y. Hwang, Seung Wan Jee, Su H. Lee, Sun B. Shim, Su J. Seo, Yong K. Kim, Chuel K. Kim, Soo Y. Choi |
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| Rok vydání: | 2005 |
| Předmět: |
Genetically modified mouse
Male Transgene Mutant Mice Transgenic Biology Cellular and Molecular Neuroscience Transactivation Mice Presenilin-2 medicine Animals Humans Testosterone Tissue Distribution Regulation of gene expression Doxycycline Amyloid beta-Peptides Behavior Animal Wnt signaling pathway Brain Molecular biology Peptide Fragments Mice Inbred C57BL Repressor Proteins Wnt Proteins Neurology Gene Expression Regulation biology.protein Molecular Medicine Female Amyloid Precursor Protein Secretases Amyloid precursor protein secretase medicine.drug Protein Binding |
| Zdroj: | Neuromolecular medicine. 8(3) |
| ISSN: | 1535-1084 |
| Popis: | Nonregulatable promoters have been mainly used to produce transgenic mice that express the human genes for Alzheimer's disease (AD). The aim of this study was to produce doubly transgenic mice expressing the regulatable tet promoter-controlled transactivator (tTA) and human mutant presenilin 2 (N141I, hPS2m) genes in order to examine the AD-related phenotypes at the basal and inducible levels. To achieve this, the first lineage of the transgenic line, expressing Tet/tTA and the second lineage of transgenic mice, expressing Tet/hPS2m, were created, and the doubly transgenic mice were produced by crossing the Tet/tTA-transgenic mice with the Tet/hPS2m-transgenic mice. The doubly transgenic mice and nontransgenic littermates were then treated with or without doxycycline. The results showed that removing doxycycline from the transgenic mice resulted in the induction of the transgene, a Wnt signaling defect, behavioral impairment, elevated amyloid-beta-42 and gamma-secretase activity compared with in the group given doxycyline. Moreover, the expression levels of the hPS2m transgene decreased gradually in the transgenic males, with clear changes becoming apparent between 2 and 4 wk of age. Castrating these males resulted in an increased expression level of the hPS2m gene. This was restored to the normal levels by treatment with testosterone. Therefore, tetregulated transgenic mice can be used to examine the effect of the basal or inducible expression levels of hPS2m on the pathology of AD at the "on/off" states at any stage of development. |
| Databáze: | OpenAIRE |
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