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Montalban, E.* ; Walle, R.* ; Castel, J.* ; Ansoult, A.* ; Hassouna, R.* ; Foppen, E.* ; Fang, X.* ; Hutelin, Z.* ; Mickus, S.* ; Perszyk, E.* ; Petitbon, A.* ; Berthelet, J.* ; Rodrigues-Lima, F.* ; Cebrian Serrano, A. ; Gangarossa, G.* ; Martin, C.* ; Trifilieff, P.* ; Bosch-Bouju, C.* ; Small, D.* ; Luquet, S.*

The addiction-susceptibility TaqIA/Ankyrin repeat and kinase domain containing 1 kinase (ANKK1) controls reward and metabolism through dopamine receptor type 2 (D2R)-expressing neurons.

Biol. Psychiatry 94, 424-436 (2023)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
BACKGROUND: A large body of evidence highlights the importance of genetic variants in the development of psychiatric and metabolic conditions. Among these, the TaqIA polymorphism is one of the most commonly studied in psychiatry. TaqIA is located in the gene that codes for the Ankyrin repeat and kinase domain containing 1 kinase (Ankk1) near the dopamine D2 dopamine receptor (D2R) gene. Homozygous expression of the A1 allele correlates with a 30 to 40% reduction of striatal D2R, a typical feature of addiction, over-eating and other psychiatric pathologies. The mechanisms by which the variant influences dopamine signaling and behavior are unknown. METHODS: Here we used transgenic and viral-mediated strategies to reveal the role of Ankk1 in the regulation of activity and functions of the striatum. RESULTS: We found that Ankk1 is preferentially enriched in striatal D2R-expressing neurons and that Ankk1 loss-of-function in dorsal and ventral striatum leads to alteration in learning, impulsivity and flexibibility resembling endophenotypes described in A1 carriers. We also observed an unsuspected role of Ankk1 in striatal D2R-expressing neurons of the ventral striatum in the regulation of energy homeostasis and documented differential nutrient partitioning in humans with or without the A1 allele. CONCLUSIONS: Overall, our data demonstrate that the Ankk1 gene is necessary for the integrity of striatal functions and reveal a new role for Ankk1 in the regulation of body metabolism.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter D2r Receptor ; Dopamine Signaling ; Eating Disorders ; Genetic Polymorphism ; Metabolism ; Reward-associated Behavior; Genetically-determined Differences; Nucleus-accumbens; Substrate Utilization; Caudate-putamen; Working-memory; Drd2 Gene; Dopamine; Polymorphism; Association; Obesity
ISSN (print) / ISBN 0006-3223
e-ISSN 1873-2402
Zeitschrift Biological Psychiatry
Quellenangaben Band: 94, Heft: 5, Seiten: 424-436 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Ste 800, 230 Park Ave, New York, Ny 10169 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Förderungen Agence Nationale de la Recherche (ANR)
FRM
Fondation des Treilles Fondation des Treilles creee par Anne Gruner Schlumberger
Federation pour la Recherche sur le Cerveau
Centre National de la Recherche Scientifique through the International Research Project Brain Health, L'Agence Nationale de la Recherche
Modern Diet and Physiology Research Center
la Fondation pour la Recherche Medicale (FRM) Project