Generation of a humanized Aß expressing mouse demonstrating aspects of Alzheimer's disease-like pathology.
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
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Péptidos beta-Amiloides
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Precursor de Proteína beta-Amiloide
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Modelos Animales de Enfermedad
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Enfermedad de Alzheimer
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Mutación
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Plasticidad Neuronal
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
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CIENCIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos