A strategy of microglia replacement alleviates microgliopathy in a CSF1R I794T hotspot mutation mouse model of CSF1R-related disorder - PubMed
5 hours ago
- #neurodegenerative disorders
- #microglia
- #CSF1R
- The CSF1R p.I794T mutation is linked to primary microgliopathy and leukoencephalopathy.
- Three Chinese probands with the CSF1R p.I794T variant were studied for clinical and neuroimaging profiles.
- A Csf1rI792T/+ knockin mouse model was created to mimic human CSF1R-related disorder (CSF1R-RD).
- The mice showed cognitive deficits, ventricular enlargement, reduced microglia, axonal spheroids, and demyelination.
- Transcriptomic analysis revealed activated and disease-associated microglia (DAM)-like phenotype in the mice.
- A microglia replacement strategy, DCMDT, was developed and tested, showing significant improvement in neuropathological deficits.
- DCMDT is proposed as a promising therapeutic approach for neurodegenerative disorders caused by microglial dysfunction.