Baglietto-Vargas, DavidForner, StefaniaCai, LenaMartini, Alessandra C.Trujillo-Estrada, LauraSwarup, VivekNguyen, Marie Minh ThuDo Huynh, KellyJavonillo, Dominic I.Tran, Kristine MinhPhan, JimmyJiang, ShanKramár, Enikö A.Nuñez-Diaz, CristinaBalderrama-Gutierrez, GabrielaGarcia, FranklinChilds, JessicaRodriguez-Ortiz, Carlos J.Garcia-Leon, Juan AntonioKitazawa, MasashiShahnawaz, MohammadMatheos, Dina P.Ma, XinyiDa Cunha, CeliaWalls, Ken C.Ager, Rahasson R.Soto, ClaudioGutierrez, AntoniaMoreno-Gonzalez, InesMortazavi, AliTenner, Andrea J.MacGregor, Grant R.Wood, MarceloGreen, Kim N.LaFerla, Frank M.2023-01-132023-01-132021-04-23Baglietto-Vargas D, Forner S, Cai L, Martini AC, Trujillo-Estrada L, Swarup V, et al. Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer's disease-like pathology. Nat Commun. 2021 Apr 23;12(1):2421http://hdl.handle.net/10668/4585The majority of Alzheimer's disease (AD) cases are late-onset and occur sporadically, however most mouse models of the disease harbor pathogenic mutations, rendering them better representations of familial autosomal-dominant forms of the disease. Here, we generated knock-in mice that express wildtype human Aβ under control of the mouse App locus. Remarkably, changing 3 amino acids in the mouse Aβ sequence to its wild-type human counterpart leads to age-dependent impairments in cognition and synaptic plasticity, brain volumetric changes, inflammatory alterations, the appearance of Periodic Acid-Schiff (PAS) granules and changes in gene expression. In addition, when exon 14 encoding the Aβ sequence was flanked by loxP sites we show that Cre-mediated excision of exon 14 ablates hAβ expression, rescues cognition and reduces the formation of PAS granules.enAtribución 4.0 InternacionalAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Periodic acid-schiffExonCognitionMutationGene expressionAlzheimer diseaseReacción del ácido peryódico de SchiffExonesCogniciónMutaciónExpresión génicaEnfermedad de AlzheimerMedical Subject Headings::Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer DiseaseMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-PeptidesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Amyloid::Amyloidogenic Proteins::Amyloid beta-Protein PrecursorMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::BrainMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression ProfilingMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genetic Research::Gene OntologyMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Base Sequence::Regulatory Sequences, Nucleic Acid::Gene Regulatory NetworksMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BLMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, TransgenicMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Nervous System Physiological Processes::Neuronal PlasticityMedical Subject Headings::Diseases::Animal Diseases::Disease Models, AnimalMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::MutationMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Acids::Acids, Noncarboxylic::Periodic AcidMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino AcidsMedical Subject Headings::Information Science::Information Science::Computing Methodologies::Software::Mobile ApplicationsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene Components::ExonsMedical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::CognitionMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expressionresearch article33893290Acceso abierto10.1038/s41467-021-22624-z2041-1723PMC8065162