UCI MODEL-AD



UCI MODEL-AD


The long-term goal of UCI MODEL-AD is to develop mouse models of late-onset Alzheimer’s Disease (LOAD) for use by the international AD research community to understand mechanisms of LOAD and to test potential therapeutics for this disease. During the past five years, the UCI-MODEL AD has generated and deeply phenotyped mice with one component of our base genetic platform in which the Aß region of the App gene was converted from the rodent to the human sequence, and has recently introduced the second component, a humanized MAPT (TAU) locus produced via gene-replacement. UCI MODEL-AD has also used CRISPR and genome replacement to model and validate nine GWAS identified LOAD risk loci and have characterized mice with each of these both on a wild-type and 5xFAD background to determine their effects on plaque generation and damage exerted on the brain in response to pathology. R Shiny apps have been created to visualize the gene-expression changes from bulk RNA-seq in these new mouse models of AD.







Gene expression time course of 5xFAD mice Cortex and hippocampal gene expression from wild-type and 5xFAD mice at 4, 8, 12, and 18 months of age. Visit 5xFAD Shiny App here From: Systematic phenotyping and characterization of the 5xFAD mouse model of Alzheimer’s disease. Scientific Data 8, 270 (2021). Click Here to Read



Gene expression time course of 3xTg-AD mice Cortex and hippocampal gene expression from wild-type and 3xTg-AD mice at 4, 12, and 18 months of age. Visit 3xTg Shiny App here From: Systematic Phenotyping and Characterization of the 3xTg-AD Mouse Model of Alzheimer’s Disease. Front. Neurosci. 15:785276. doi: 10.3389/fnins.2021.785276. Click Here to Read



Gene expression time course of hAβ-KI mice Hippocampal gene expression from wild-type and hAβ-KI mice at 4, 12, 18, and 24 months of age. Visit hAβ-KI Shiny App here From: Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer’s disease-like pathology. Nature Communications, 2021 Apr 23;12(1):2421. Click Here to Read



Effects of genetic diversity on gene expression changes in Collaborative Cross backgrounds in the presence and absence of the 5xFAD transgene 5xFAD mice were crossed with CC002, CC006, CC013, CC017, CC037, and CC041 to generate Wild-Type and 5xFAD F1’s. These were then aged to 4 and 12 months of age. Visit CClines Shiny App here



Effects of Trem2*R47H variant on hippocampal gene expression in 5xFAD mice 5xFAD mice were crossed with Trem2*R47H mice, and aged to 4, and 12, months of age. Gene expression data is available from hippocampus. Visit 5xFAD::Trem2 Shiny App here



Effects of Picalm*H458R variant on hippocampal gene expression in 5xFAD mice 5xFAD mice were crossed with Picalm*H458R mice, and aged to 4, and 12, months of age. Gene expression data is available from hippocampus. Visit 5xFAD::Picalm Shiny App here



Effects of Abca7*V1599M variant on hippocampal gene expression in 5xFAD mice 5xFAD mice were crossed with Abca7*V1599M mice, and aged to 4, and 12, months of age. Gene expression data is available from hippocampus. Visit 5xFAD::Abca7 Shiny App here



Effects of Abi3*S209F variant on hippocampal gene expression in 5xFAD mice 5xFAD mice were crossed with Abi3*S209F mice, and aged to 4, and 12, months of age. Gene expression data is available from hippocampus. Visit 5xFAD::Abi3 Shiny App here