Neuron-specific deletion of both ADAR1 p110 and p150 in mice activated type-I interferon, caused choroid-plexus and ependymal hypoplasia, ventricular obstruction and early postnatal death. Restoring p150 or deleting MDA5 largely normalised interferon signalling and obstruction but did not rescue survival, indicating essential functions beyond the MDA5 pathway.
Key findings
- Neuronal ADAR1 loss elevated ISGs, produced ventricular obstruction associated with choroid-plexus/ependymal hypoplasia and gliosis, and caused early death. p150 restoration or MDA5 deletion improved ISGs and obstruction but not survival; restoring only editing-independent p110 function was also insufficient.
Why this matters globally
The findings suggest that ADAR1-related encephalopathy may combine interferon-driven and neuron-intrinsic mechanisms, so suppressing one immune pathway may be insufficient.
Thai researcher contribution
Tuangtong Vongpipatana is affiliated with Kasetsart University's Department of Biochemistry and the University of Osaka's RNA Biology and Neuroscience unit, reflecting Thai-Japanese collaboration.
Limitations to consider
A severe mouse knockout does not model every patient mutation. Neuronal subtype, deletion timing and Cre efficiency may shape the phenotype; animal numbers and sex are absent from the abstract; and failed survival rescue may reflect irreversible developmental injury.