Expression of mutant β2 nicotinic receptors during development is crucial for epileptogenesis

Irene Manfredi, Alessia D. Zani, Luca Rampoldi, Simona Pegorini, Ilenia Bernascone, Milena Moretti, Cecilia Gotti, Laura Croci, G. Giacomo Consalez, Luigi Ferini-Strambi, Mariaelvina Sala, Linda Pattini, Giorgio Casari

Research output: Contribution to journalArticlepeer-review


Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a focal form of epilepsy characterized by seizures occurring during non-REM sleep. We have developed and characterized the first mouse model for ADNFLE type III carrying the V287L mutation of the β2 subunit of neuronal nicotinic receptor. Mice expressing mutant receptors show a spontaneous epileptic phenotype by electroencephalography with very frequent interictal spikes and seizures. Expression of the mutant β2 subunit is driven by a neuronal-specific tetracycline-controlled promoter, which allows planned silencing of transgene expression in a reversible fashion and tracking the involvement of mutant receptor in crucial phases of epileptogenesis. We found that restricted silencing during development is sufficient to prevent the occurrence of epileptic seizures in adulthood. Our data indicate that mutant nicotinic receptors are responsible for abnormal formation of neuronal circuits and/or long-lasting alteration of network assembly in the developing brain, thus leading to epilepsy.

Original languageEnglish
Pages (from-to)1075-1088
Number of pages14
JournalHuman Molecular Genetics
Issue number6
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology


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