Deletion of SERF2 in mice delays embryonic development and alters amyloid deposit structure in the brain
| Autor: | Esther Stroo, Leen Janssen, Olga Sin, Wytse Hogewerf, Mirjam Koster, Liesbeth Harkema, Sameh A Youssef, Natalie Beschorner, Anouk HG Wolters, Bjorn Bakker, Lore Becker, Lilian Garrett, Susan Marschall, Sabine M Hoelter, Wolfgang Wurst, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe de Angelis, Amantha Thathiah, Floris Foijer, Bart van de Sluis, Jan van Deursen, Matthias Jucker, Alain de Bruin, Ellen AA Nollen |
|---|---|
| Přispěvatelé: | Pathology, Dep Biomolecular Health Sciences, Pathobiologie |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: |
Beta fibrils
Knockout Health Toxicology and Mutagenesis Precursor protein Alpha-synuclein aggregation metabolism [Amyloid beta-Peptides] Plant Science Biochemistry Genetics and Molecular Biology (miscellaneous) Amyloid/metabolism In-vitro Mice Platform ddc:570 Embryonic Development/genetics Humans Animals SERF2 protein human Amyloid beta-Peptides/metabolism Parkinsons-disease Plaque Mice Knockout Amyloid beta-Peptides Ecology metabolism [Mammals] Intracellular Signaling Peptides and Proteins genetics [Embryonic Development] Cell-cycle metabolism [Plaque Amyloid] Intracellular Signaling Peptides and Proteins/metabolism metabolism [Brain] Mutation Serf2 protein mouse Brain/embryology Tau Onset alzheimers-disease metabolism [Intracellular Signaling Peptides and Proteins] |
| Zdroj: | Life science alliance 6(7), e202201730 (2023). doi:10.26508/lsa.202201730 |
| DOI: | 10.26508/lsa.202201730 |
| Popis: | In age-related neurodegenerative diseases, like Alzheimer’s and Parkinson’s, disease-specific proteins become aggregation-prone and form amyloid-like deposits. Depletion of SERF proteins ameliorates this toxic process in worm and human cell models for diseases. Whether SERF modifies amyloid pathology in mammalian brain, however, has remained unknown. Here, we generated conditionalSerf2knockout mice and found that full-body deletion ofSerf2delayed embryonic development, causing premature birth and perinatal lethality. Brain-specificSerf2knockout mice, on the other hand, were viable, and showed no major behavioral or cognitive abnormalities. In a mouse model for amyloid-β aggregation, brain depletion ofSerf2altered the binding of structure-specific amyloid dyes, previously used to distinguish amyloid polymorphisms in the human brain. These results suggest thatSerf2depletion changed the structure of amyloid deposits, which was further supported by scanning transmission electron microscopy, but further study will be required to confirm this observation. Altogether, our data reveal the pleiotropic functions of SERF2 in embryonic development and in the brain and support the existence of modifying factors of amyloid deposition in mammalian brain, which offer possibilities for polymorphism-based interventions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|