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

Esther Stroo, Leen Janssen, Olga Sin, Wytse Hogewerf, Mirjam Koster, Liesbeth Harkema, Sameh A. Youssef, Natalie Beschorner, Anouk H.G. 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 FoijerBart van de Sluis, Jan van Deursen, Matthias Jucker, Alain de Bruin, Ellen A.A. Nollen

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 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 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-β 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 possibilities for polymorphism-based interventions.

Original languageEnglish
Article numbere202201730
JournalLife Science Alliance
Volume6
Issue number7
DOIs
StatePublished - Jul 2023

Fingerprint

Dive into the research topics of 'Deletion of SERF2 in mice delays embryonic development and alters amyloid deposit structure in the brain'. Together they form a unique fingerprint.

Cite this