PT - JOURNAL ARTICLE AU - Stroo, Esther AU - Janssen, Leen AU - Sin, Olga AU - Hogewerf, Wytse AU - Koster, Mirjam AU - Harkema, Liesbeth AU - Youssef, Sameh A AU - Beschorner, Natalie AU - Wolters, Anouk HG AU - Bakker, Bjorn AU - Becker, Lore AU - Garrett, Lilian AU - Marschall, Susan AU - Hoelter, Sabine M AU - Wurst, Wolfgang AU - Fuchs, Helmut AU - Gailus-Durner, Valerie AU - Hrabe de Angelis, Martin AU - Thathiah, Amantha AU - Foijer, Floris AU - van de Sluis, Bart AU - van Deursen, Jan AU - Jucker, Matthias AU - de Bruin, Alain AU - Nollen, Ellen AA TI - Deletion of SERF2 in mice delays embryonic development and alters amyloid deposit structure in the brain AID - 10.26508/lsa.202201730 DP - 2023 Jul 01 TA - Life Science Alliance PG - e202201730 VI - 6 IP - 7 4099 - https://www.life-science-alliance.org/content/6/7/e202201730.short 4100 - https://www.life-science-alliance.org/content/6/7/e202201730.full SO - Life Sci. Alliance2023 Jul 01; 6 AB - 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.