![]() While App NL-G-F rats do not develop neurofibrillary tangles, at least through 22 months of age, they do exhibit age-dependent increases in tau phosphorylation and aggregation and pathological changes in the conformation of tau. Plaque burden increased with age, and progressed more rapidly in females than males, particularly after 6 months. AmyloidĪmyloid deposition was detected in homozygous App NL-G-F rats as young as 1 month old and in heterozygous animals as early as 4 months. The description below refers to male rats homozygous for the mutant App allele, unless stated otherwise. Notably, these animals exhibit pronounced neuron loss in the hippocampus and cortex. Although neurofibrillary tangles are not seen through 22 months of age, increased tau phosphorylation, aggregation, and conformational changes are observed, as are astrogliosis, microgliosis, and synapse loss. Amyloid plaques appear as early as one month in homozygous knock-in brains. ![]() Knock-in rats express normal levels of full-length APP and APP C-terminal fragments (i.e., levels comparable to wild-type controls). This rat line, created using CRISPR/Cas9 technology, carries a humanized Aβ sequence and three Alzheimer’s-linked mutations (Swedish, KM670/671NL Arctic, E693G and Iberian, I716F) in the endogenous rat App gene ( Pang et al., 2022). Species: Rat Genes: App Mutations: APP K670_M671delinsNL (Swedish), APP E693G (Arctic), APP I716F (Iberian) Modification: App: Knock-In Disease Relevance: Alzheimer's Disease Strain Name: N/A Genetic Background: Sprague Dawley Availability: Available through Bai Lu. ![]()
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