Fiche publication
Date publication
janvier 2024
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr HERAULT Yann
,
Dr GOGL Gergo
Tous les auteurs :
Jimenez-Armijo A, Morkmued S, Ahumada JT, Kharouf N, de Feraudy Y, Gogl G, Riet F, Niederreither K, Laporte J, Birling MC, Selloum M, Herault Y, Hernandez M, Bloch-Zupan A
Lien Pubmed
Résumé
Kohlschütter-Tönz syndrome (KTS) is a rare autosomal recessive disorder characterized by severe intellectual disability, early-onset epileptic seizures, and amelogenesis imperfecta. Here, we present a novel Rogdi mutant mouse deleting exons 6-11- a mutation found in KTS patients disabling ROGDI function. This Rogdi mutant model recapitulates most KTS symptoms. Mutants displayed pentylenetetrazol-induced seizures, confirming epilepsy susceptibility. Spontaneous locomotion and circadian activity tests demonstrate Rogdi mutant hyperactivity mirroring patient spasticity. Object recognition impairment indicates memory deficits. Rogdi mutant enamel was markedly less mature. Scanning electron microscopy confirmed its hypomineralized/hypomature crystallization, as well as its low mineral content. Transcriptomic RNA sequencing of postnatal day 5 lower incisors showed downregulated enamel matrix proteins Enam, Amelx, and Ambn. Enamel crystallization appears highly pH-dependent, cycling between an acidic and neutral pH during enamel maturation. Rogdi teeth exhibit no signs of cyclic dental acidification. Additionally, expression changes in Wdr72, Slc9a3r2, and Atp6v0c were identified as potential contributors to these tooth acidification abnormalities. These proteins interact through the acidifying V-ATPase complex. Here, we present the Rogdi mutant as a novel model to partially decipher KTS pathophysiology. Rogdi mutant defects in acidification might explain the unusual combination of enamel and rare neurological disease symptoms.
Mots clés
Humans, Animals, Mice, Amelogenesis Imperfecta, genetics, Epilepsy, Dementia, Seizures, Mutation, Tooth Abnormalities, Membrane Proteins, genetics, Nuclear Proteins, genetics
Référence
Sci Rep. 2024 01 3;14(1):445
