TY  - JOUR
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.
JO  - Life science alliance
VL  - 6
IS  - 7
SN  - 2575-1077
CY  - Heidelberg
PB  - EMBO Press
M1  - DZNE-2023-00511
SP  - e202201730
PY  - 2023
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.
KW  - Brain: embryology
KW  - Mice
KW  - Humans
KW  - Animals
KW  - Plaque, Amyloid: metabolism
KW  - Brain: metabolism
KW  - Amyloid beta-Peptides: metabolism
KW  - Mice, Knockout
KW  - Embryonic Development: genetics
KW  - Mammals: metabolism
KW  - Intracellular Signaling Peptides and Proteins: metabolism
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - SERF2 protein, human (NLM Chemicals)
KW  - Intracellular Signaling Peptides and Proteins (NLM Chemicals)
KW  - Serf2 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:37130781
C2  - pmc:PMC10155860
DO  - DOI:10.26508/lsa.202201730
UR  - https://pub.dzne.de/record/257883
ER  -