Characterization of Human 82-kDa Choline Acetyltransferase expression in a newly developed Transgenic Mouse Model

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Vanvaerenbergh, Silke M
Human 82-kDa Choline Acetyltransferase; Nkx2.1; Cre-LoxP System; Transgenic Mice; Alzheimer's Disease; Molecular and Cellular Neuroscience
article description
Expression of human 82-kDa choline acetyltransferase (ChAT) protein in nuclei of cultured neurons from Alzheimer’s disease model APP/PS1 transgenic mice results in a reduction in Aβ release, suggesting a protective role. This thesis characterizes the expression of human 82-kDa ChAT in 82-hChAT;NkCre transgenic mice by PCR-based examination of genomic DNA and localization of the protein in mice brains. First, I demonstrate in a cultured cell model that Cre recombinase-mediated excision of a floxed LacZ gene is necessary for human 82-kDa ChAT protein expression from pcCALL2:82-ChAT, the plasmid used to create founder transgenic mice. Second, I confirmed that human 82-kDa ChAT protein is expressed in the brain of 82-hChAT;NkCre but not 82-hChAT mice. This protein is localized to nuclei of neurons in the basal forebrain and medial cerebral cortex. These findings indicate that we successfully generated transgenic mice that have neuron-specific expression of human 82-kDa ChAT protein in Nkx2.1-Cre driven areas.