This ES cell line carries a random insertion of human, mutated APP driven by human PDGFB promoter; the transgene was found to be inserted into the Zbtb20 gene. The APP variants are commonly referred to as the Swedish and the Indiana mutations

Hemizygous: These transgenic mice express a mutant form of the human amyloid protein precursor bearing both the Swedish (K670N/M671L) and the Indiana (V717F) mutations (APPSwInd). Expression of the transgenic insert is directed by the human platelet-derived growth factor beta polypeptide (PDGFB) promoter. Hemizygotes express immunodetectable transgene product in cerebral neurons, with the highest level of expression occurring in the neocortex and hippocampus. Enzyme-linked immunosorbent assay (ELISA) analysis reveals approximate total amyloid beta peptides and 42 amino acid length amyloid beta peptides in neocortical and hippocampal tissue from mutant mice. At five to seven months of age diffuse amyloid beta peptides deposition in the dentate gyrus and neocortex forms. Amyloid deposition is progressive with all transgenic mice exhibiting plaques by age eight to 10 months. Video-EEG monitoring of 4 to 7-month-old hemizygous transgenic mice, N10+ on the C57BL/6J background, reveals hippocampal hyperexcitability and cortical and hippocampal spontaneous nonconvulsive seizures. The mice are immobile, with no myoclonic behavior observed, during the non-convulsive electroencephalographic seizures. Pentylenetetrazole-induced seizures have earlier onset, are more severe and result in more frequent deaths (50% develop fatal status epilepticus) than wild-type controls (PMID:17785178). This mutant mouse strain represents a model that may be useful in studies of the pathogenesis of Familial Alzheimer's Disease and possible therapeutic treatments. Pups born of carrier females have shown an increased mortality rate in our colonies. The Submitting Researcher has observed an approximately 15% mortality rate in the first 6 months of life.

Lennart Mucke, Ph.D., Gladstone Institute of Neurological Disease

A transgenic construct containing the mutant human amyloid protein precursor APPSwInd under the control of human platelet-derived growth factor beta polypeptide, simian sarcoma viral (v-sis) oncogene homolog, (PDGFB) promoter, was injected into (C57BL/6 x DBA/2)F2 one-cell embryos. Heterozygous founder animals were bred to (C57BL/6 x DBA/2)F1 mice. The resulting transgenic mice were backcrossed for 12 generations on the C57BL/6J background.