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Generation of a humanized Aß expressing mouse demonstrating aspects of Alzheimer's disease-like pathology.
Baglietto-Vargas, David; Forner, Stefania; Cai, Lena; Martini, Alessandra C; Trujillo-Estrada, Laura; Swarup, Vivek; Nguyen, Marie Minh Thu; Do Huynh, Kelly; Javonillo, Dominic I; Tran, Kristine Minh; Phan, Jimmy; Jiang, Shan; Kramár, Enikö A; Nuñez-Diaz, Cristina; Balderrama-Gutierrez, Gabriela; Garcia, Franklin; Childs, Jessica; Rodriguez-Ortiz, Carlos J; Garcia-Leon, Juan Antonio; Kitazawa, Masashi; Shahnawaz, Mohammad; Matheos, Dina P; Ma, Xinyi; Da Cunha, Celia; Walls, Ken C; Ager, Rahasson R; Soto, Claudio; Gutierrez, Antonia; Moreno-Gonzalez, Ines; Mortazavi, Ali; Tenner, Andrea J; MacGregor, Grant R; Wood, Marcelo; Green, Kim N; LaFerla, Frank M.
Afiliación
  • Baglietto-Vargas D; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Forner S; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
  • Cai L; Department of Cell Biology, Genetic and Physiology, Faculty of Sciences, Instituto de Investigacion Biomedica de Malaga-IBIMA, Networking Research Center on Neurodegenerative Diseases (CIBERNED), University of Malaga, Malaga, Spain.
  • Martini AC; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Trujillo-Estrada L; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Swarup V; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Nguyen MMT; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Do Huynh K; Department of Cell Biology, Genetic and Physiology, Faculty of Sciences, Instituto de Investigacion Biomedica de Malaga-IBIMA, Networking Research Center on Neurodegenerative Diseases (CIBERNED), University of Malaga, Malaga, Spain.
  • Javonillo DI; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Tran KM; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
  • Phan J; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Jiang S; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Kramár EA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Nuñez-Diaz C; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Balderrama-Gutierrez G; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Garcia F; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Childs J; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Rodriguez-Ortiz CJ; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
  • Garcia-Leon JA; Department of Cell Biology, Genetic and Physiology, Faculty of Sciences, Instituto de Investigacion Biomedica de Malaga-IBIMA, Networking Research Center on Neurodegenerative Diseases (CIBERNED), University of Malaga, Malaga, Spain.
  • Kitazawa M; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Shahnawaz M; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Matheos DP; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
  • Ma X; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Da Cunha C; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
  • Walls KC; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Ager RR; Division of Occupational and Environmental Medicine, Department of Medicine. Center for Occupational and Environmental Health (COEH), University of California, Irvine, CA, USA.
  • Soto C; Department of Cell Biology, Genetic and Physiology, Faculty of Sciences, Instituto de Investigacion Biomedica de Malaga-IBIMA, Networking Research Center on Neurodegenerative Diseases (CIBERNED), University of Malaga, Malaga, Spain.
  • Gutierrez A; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Moreno-Gonzalez I; Division of Occupational and Environmental Medicine, Department of Medicine. Center for Occupational and Environmental Health (COEH), University of California, Irvine, CA, USA.
  • Mortazavi A; The Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Tenner AJ; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • MacGregor GR; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
  • Wood M; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Green KN; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • LaFerla FM; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
Nat Commun ; 12(1): 2421, 2021 04 23.
Article en En | MEDLINE | ID: mdl-33893290
ABSTRACT
The 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 Aß under control of the mouse App locus. Remarkably, changing 3 amino acids in the mouse Aß 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 Aß sequence was flanked by loxP sites we show that Cre-mediated excision of exon 14 ablates hAß expression, rescues cognition and reduces the formation of PAS granules.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Encéfalo / Péptidos beta-Amiloides / Precursor de Proteína beta-Amiloide / Modelos Animales de Enfermedad / Enfermedad de Alzheimer / Mutación / Plasticidad Neuronal Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Encéfalo / Péptidos beta-Amiloides / Precursor de Proteína beta-Amiloide / Modelos Animales de Enfermedad / Enfermedad de Alzheimer / Mutación / Plasticidad Neuronal Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos