Mouse Genome Informatics
phenotype observed in females
phenotype observed in males
N normal phenotype
• low level of mortality is displayed by transgenic mice, with 2 females (5-7 months of age) and 3 males (17 months of age) dying during course of study, compared to 0 controls

• bodyweights of males and females are reduced by ~15% compared to wild-type littermates

• transgenic mice show no dysfunction of motor skills, motor impairment, or paralysis up to 18 months of age
• mice spend more time in the open arms of an elevated-plus maze compared to wild-type littermate controls
• over a 4-day period, transgenic mice show significant delay in learning the location of the hidden platform in the Morris water maze task on days 2 and 3 compared to wild-type controls
• spatial memory is also significantly impaired in mice aged 10-14 months compared to wild-type controls

nervous system
• in 6-7 month old mice, LTP remains normal
• by 3 months of age, abnormal MAPT (tau) species are observed early in CA1 pyramidal layer of hippocampus and spreading to detante gyrus and CA3; also seen in striatum, olfactory bulb, occipital cortex, amygdala, ventral thalamic nuclei, and deep layers of entorhinal cortex
• a slight reduction in number and size of tau-positive neurons in frontal cortex, CA1 and CA3 regions, and in neurites and fiber tracts of entire hippocampus is observed in mice >12 months of age
• ghost tangles are detected in CA1 by 12 months; in pyramidal neurons, fibrillary inclusions are ~19.4 nm in diameter, with largest having diameter of 31.9 nm, showing regular constrictions every ~129 nm
• before abnormal tau species are detected in neuron soma, they are detected in axonal tracts and neurites; older mice show intracellular inclusions in neuronal perikarya and in proximal portions of dendrites
• mice >12 months of age show hyperphosphorylation and pathological tau phosphorylation, formation of neurofibrillary tangle-like inclusions, tau filaments and ghost tangles (Alzheimer disease-like pathology)
• at 6 months of age, neurons containing tau deposits are detected in the pyramidal cell layer of the CA1 region and in the prefrontal cortex; number increases with age, and by 12 months, such neurons are found in the dentate gyrus, CA3 region, and amygdala
• increase in number of glial cells is detected in hippocampal hilus, cerebral cortex, corpus callosum, CA1, and CA3 region in aged mice
• neurons containing pathological tau species increases with age
• synaptic function (transmission) is decreased by 80% relative to wild-type
• synaptic excitability is reduced in 14-15 month animals; mean amplitude of EPSPs at high stimulation intensity is 0.289 mV vs 1.24 mV in wild-type mice

Mouse Models of Human Disease
Alzheimer Disease; AD 104300 J:111982