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The Rogdi knockout mouse is a model for Kohlschütter-Tönz syndrome.
Jimenez-Armijo, Alexandra; Morkmued, Supawich; Ahumada, José Tomás; Kharouf, Naji; de Feraudy, Yvan; Gogl, Gergo; Riet, Fabrice; Niederreither, Karen; Laporte, Jocelyn; Birling, Marie Christine; Selloum, Mohammed; Herault, Yann; Hernandez, Magali; Bloch-Zupan, Agnès.
Afiliação
  • Jimenez-Armijo A; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS- UMR7104, Université de Strasbourg, Illkirch, France.
  • Morkmued S; Pediatrics Division, Department of Preventive Dentistry, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand.
  • Ahumada JT; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS- UMR7104, Université de Strasbourg, Illkirch, France.
  • Kharouf N; Laboratoire de Biomatériaux et Bioingénierie, Inserm UMR_S 1121, Université de Strasbourg, Strasbourg, France.
  • de Feraudy Y; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS- UMR7104, Université de Strasbourg, Illkirch, France.
  • Gogl G; Department of Neuropediatrics, Strasbourg University Hospital, Strasbourg, France.
  • Riet F; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS- UMR7104, Université de Strasbourg, Illkirch, France.
  • Niederreither K; CNRS, INSERM, CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS), Université de Strasbourg, Illkirch, France.
  • Laporte J; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS- UMR7104, Université de Strasbourg, Illkirch, France.
  • Birling MC; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS- UMR7104, Université de Strasbourg, Illkirch, France.
  • Selloum M; CNRS, INSERM, CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS), Université de Strasbourg, Illkirch, France.
  • Herault Y; CNRS, INSERM, CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS), Université de Strasbourg, Illkirch, France.
  • Hernandez M; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS- UMR7104, Université de Strasbourg, Illkirch, France.
  • Bloch-Zupan A; CNRS, INSERM, CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS), Université de Strasbourg, Illkirch, France.
Sci Rep ; 14(1): 445, 2024 01 03.
Article em En | MEDLINE | ID: mdl-38172607
ABSTRACT
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Anormalidades Dentárias / Demência / Epilepsia / Amelogênese Imperfeita Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Anormalidades Dentárias / Demência / Epilepsia / Amelogênese Imperfeita Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article