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. The transgene integrated into chromosome 16 causing a 40.7 Kb deletion in an intron of the Zbtb20 (zinc finger and BTB domain containing 20) gene. Founder line 20 has a copy number of greater than 10. 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 dendate gyrus and neocortex forms. Amyloid deposition is progressive with all transgenic mice exhibiting plaques by age eight to 10 months. Pups born of carrier females have shown an increased mortality rate in our colonies. The Donating Researcher has observed an approximately 15% mortality rate in the first 6 months of life. 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 wildtype controls (Palop et al. Neuron 2007). 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.

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).  They show progressive amyloid deposition as they age. 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.

This strain is hosted by NIH's MMRRC, which partners with JAX for the distribution of this and other strains. For additional information and to purchase, please visit the MMRRC site.