Global huntingtin knockout in adult mice leads to fatal neurodegeneration that spares the pancreas.
Life Sci Alliance
; 7(9)2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-39054288
ABSTRACT
Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG tract in the huntingtin (HTT) gene, leading to toxic gains of function. HTT-lowering treatments are in clinical trials, but the risks imposed are unclear. Recent studies have reported on the consequences of widespread HTT loss in mice, where one group described early HTT loss leading to fatal pancreatitis, but later loss as benign. Another group reported no pancreatitis but found widespread neurological phenotypes including subcortical calcification. To better understand the liabilities of widespread HTT loss, we knocked out Htt with two separate tamoxifen-inducible Cre lines. We find that loss of HTT at 2 mo of age leads to progressive tremors and severe subcortical calcification at examination at 14 mo of age but does not result in acute pancreatitis or histological changes in the pancreas. We, in addition, report that HTT loss is followed by sustained induction of circulating neurofilament light chain. These results confirm that global loss of HTT in mice is associated with pronounced risks, including progressive subcortical calcification and neurodegeneration.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pâncreas
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Doença de Huntington
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Camundongos Knockout
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Modelos Animais de Doenças
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Proteína Huntingtina
Limite:
Animals
Idioma:
En
Revista:
Life Sci Alliance
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos