The number of IBA1-positive microglia surrounding each plaque is greater in CAST.APP/PS1 compared with B6.APP/PS1, as is the number of plaque-associated microglia that express the proliferation marker KI-67. Plaque-associated microgliosis is present in 8-month CAST.APP/PS1 brains. Pronounced cerebral amyloid angiopathy is seen in CAST.APP/PS1 mice, a pathological feature that is absent from B6.APP/PS1 animals. Compared with B6.APP/PS1 mice, CAST.APP/PS1 mice have fewer plaques and particularly lack small plaques. Thioflavin S-positive amyloid plaques are present in the cortex and hippocampus by 8 months of age, with more severe plaque pathology in females than in males.
However, female CAST.APP/PS1 mice have higher levels of Aβ42 in their brains than do B6.APP/PS1 females. APP protein levels were also similar in CAST.APP/PS1 and B6.APP/PS1 brains. Levels of the transgenic APPswe and PSEN1dE9 transcripts in brain were similar between the three wild-derived strains and APPswe/PSEN1dE9 on a C57BL6 background (“B6.APP/PS1”). The CAST strain differs from the widely used C57BL6 inbred strain at around 23 million sites in the genome.įor the initial characterization of these mice, a behavioral battery was conducted on animals between 6 and 8 months of age, after which tissue was harvested for neuropathological and transcriptomic analyses (The other two models, WSB.APP/PS1 and PWK.APP/PS1, are described in detail elsewhere.) The forebears of the CAST strain ( Mus mus castaneus) were trapped in Thailand. CAST.APP/PS1 mice are among a set of models created by backcrossing APPswe/PSEN1dE9 mice to three different “wild-derived” strains-inbred strains created in the laboratory from subspecies of house mice caught in the wild less than 50 years ago ( Onos et al., 2019). In an effort to mimic the genetic diversity seen in human populations, scientists have crossed popular transgenic mouse models of Alzheimer’s disease with mice of various genetic backgrounds (see news news). Species: Mouse Genes: APP, PSEN1 Mutations: APP KM670/671NL (Swedish), PSEN1: deltaE9 Modification: APP: Transgenic PSEN1: Transgenic Disease Relevance: Alzheimer's Disease Strain Name: CAST.Cg-Tg(APPswe,PSEN1dE9)85Dbo/How Genetic Background: CAST/EiJ Availability: Available from The Jackson Laboratory, Stock #25973.