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Published on: November 10, 2008
Deletion of SERF2 in mice delays embryonic development and alters amyloid deposit structure in the brain
Esther Stroo1, Leen Janssen2, Olga Sin1,3
1European Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
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.
Insights
SERF2 protein depletion impacts embryonic development and alters amyloid structure in mouse brains. This suggests SERF2 influences amyloid deposition, offering potential therapeutic targets for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Age-related neurodegenerative diseases, such as Alzheimer's and Parkinson's, involve protein aggregation into amyloid deposits.
- SERF proteins are known to mitigate toxic aggregation processes in simpler models.
- The role of SERF proteins in mammalian brain amyloid pathology was previously uncharacterized.
Purpose of the Study:
- To investigate the function of SERF2 in mammalian brain amyloid pathology.
- To determine if SERF2 influences the structure of amyloid deposits in vivo.
- To explore the developmental roles of SERF2.
Main Methods:
- Generation of conditional Serf2 knockout mice (full-body and brain-specific).
- Assessment of embryonic development, viability, and neurobehavioral phenotypes.
- Analysis of amyloid-β aggregation using amyloid dyes and scanning transmission electron microscopy in a mouse model.
Main Results:
- Full-body Serf2 deletion resulted in developmental delays and perinatal lethality.
- Brain-specific Serf2 knockout mice were viable with no significant cognitive or behavioral deficits.
- Depletion of Serf2 in the brain altered amyloid deposit structure, indicated by changes in dye binding and preliminary electron microscopy data.
Conclusions:
- SERF2 exhibits pleiotropic functions, affecting both embryonic development and brain amyloid structure.
- The findings support the existence of endogenous factors that modify amyloid deposition in the mammalian brain.
- Targeting SERF2 or related pathways may offer novel strategies for intervening in amyloid polymorphism-based diseases.
