Position effect variegations and brain-specific silencing in transgenic mice overexpressing human acetylcholinesterase variants

Position effect variegations as well as brain-specific silencing were observed in novel transgenic mouse pedigrees expressing human acetylcholinesterase (AChE) variants. Muscle AChE activities varied between 1.6- and 350-fold of control in these lines, one carrying insertion- inactivated lnE6-AChE and two with 'readthrough' I4/E5 AChE, all under control of the ubiquitous CMV promoter. In contrast, brain AChE levels remained within a range of 1.5-fold over control, suggesting an upper limit of brain AChE which is compatible with life.