Journal Article

DZNE-2023-00511

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Deletion of SERF2 in mice delays embryonic development and alters amyloid deposit structure in the brain.

Stroo, E. ; Janssen, L. ; Sin, O. ; Hogewerf, W. ; Koster, M. ; Harkema, L. ; Youssef, S. A. ; Beschorner, N. ; Wolters, A. H. ; Bakker, B. ; Becker, L. ; Garrett, L. ; Marschall, S. ; Hoelter, S. M. ; Wurst, W.DZNE* ; Fuchs, H. ; Gailus-Durner, V. ; Hrabe de Angelis, M. ; Thathiah, A. ; Foijer, F. ; van de Sluis, B. ; van Deursen, J. ; Jucker, M. ; de Bruin, A. ; Nollen, E. A.

2023
EMBO Press Heidelberg

This record in other databases:    

Please use a persistent id in citations: doi:10.26508/lsa.202201730

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.

Keyword(s): Brain: embryology (MeSH) ; Mice (MeSH) ; Humans (MeSH) ; Animals (MeSH) ; Plaque, Amyloid: metabolism (MeSH) ; Brain: metabolism (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Mice, Knockout (MeSH) ; Embryonic Development: genetics (MeSH) ; Mammals: metabolism (MeSH) ; Intracellular Signaling Peptides and Proteins: metabolism (MeSH) ; Amyloid beta-Peptides ; SERF2 protein, human ; Intracellular Signaling Peptides and Proteins ; Serf2 protein, mouse

---

Contributing Institute(s):

1. Genome Engineering (AG Wurst)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2023

---

Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---