Deletion of SERF2 in mice delays embryonic development and alters amyloid deposit structure in the brain

Stroo, Esther; Janssen, Leen; Sin, Olga; Hogewerf, Wytse; Koster, Mirjam; Harkema, Liesbeth; Youssef, Sameh A.; Beschorner, Natalie; Wolters, Anouk H. G.; Bakker, Bjorn; Becker, Lore; Garrett, Lilian; Marschall, Susan; Hoelter, Sabine M.; Wurst, Wolfgang; Fuchs, Helmut; Gailus-Durner, Valerie; Hrabe de Angelis, Martin; Thathiah, Amanth; Foijer, Floris; Sluis, Bart van de; Deursen, Jan van; Jucker, Matthias; Brun, Alain de und Nollen, Ellen A. A. (2023): Deletion of SERF2 in mice delays embryonic development and alters amyloid deposit structure in the brain. In: Life Science Alliance, Bd. 6, Nr. 7, e202201730

Abstract

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 pro-teins 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 conditional Serf2 knockout mice and found that full -body deletion of Serf2 delayed embryonic development, causing premature birth and perinatal lethality. Brain-specific Serf2 knockout mice, on the other hand, were viable, and showed no major behavioral or cognitive abnormalities. In a mouse model for amyloid-beta aggregation, brain depletion of Serf2 altered the binding of structure-specific amyloid dyes, previously used to distinguish amyloid polymorphisms in the human brain. These results suggest that Serf2 depletion 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 possi-bilities for polymorphism-based interventions.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198