The ANKK1 gene associated with addictions is expressed in astroglial cells and upregulated by apomorphine.
BACKGROUND
TaqIA, the most widely analyzed genetic polymorphism in addictions, has traditionally been considered a gene marker for association with D2 dopamine receptor gene (DRD2). TaqIA is located in the coding region of the ANKK1 gene that overlaps DRD2 and encodes a predicted kinase ANKK1. The ANKK1 protein nonetheless had yet to be identified. This study examined the ANKK1 expression pattern as a first step to uncover the biological bases of TaqIA-associated phenotypes.


METHODS
Northern blot and quantitative reverse-transcriptase polymerase chain reaction analyses were performed to analyze the ANKK1 mRNA. To study ANKK1 protein expression, we developed two polyclonal antibodies to a synthetic peptides contained in the putative Ser/Thr kinase domain.


RESULTS
We demonstrate that ANKK1 mRNA and protein were expressed in the adult central nervous system (CNS) in human and rodents, exclusively in astrocytes. Ankk1 mRNA level in mouse astrocyte cultures was upregulated by apomorphine, suggesting a potential relationship with the dopaminergic system. Developmental studies in mice showed that ANKK1 protein was ubiquitously located in radial glia in the CNS, with an mRNA expression pick around embryonic Day 15. This time expression pattern coincided with that of the Drd2 mRNA. On induction of differentiation by retinoic acid, a sequential expression was found in human neuroblastoma, where ANKK1 was expressed first, followed by that of DRD2. An opposite time expression pattern was found in rat glioma.


CONCLUSIONS
Spatial and temporal regulation of the expression of ANKK1 suggest an involvement of astroglial cells in TaqIA-related neuropsychiatric phenotypes both during development and adult life.
Department of Psychiatry, Hospital Universitario 12 de Octubre, Madrid, Spain. jhoenicka@gmail.com
Janet
J
Hoenicka
Adolfo
A
Quiñones-Lombraña
Laura
L
España-Serrano
Ximena
X
Alvira-Botero
Leonor
L
Kremer
Rocío
R
Pérez-González
Roberto
R
Rodríguez-Jiménez
Miguel Angel
MA
Jiménez-Arriero
Guillermo
G
Ponce
Tomás
T
Palomo
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology* / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D004622:Embryo, Mammalian; D005910:Glioma; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment / Q000379:methods; D020539:Sequence Analysis, Protein; D019966:Substance-Related Disorders / Q000235:genetics*; D013469:Sulpiride / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
D018491:Dopamine Agonists; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D014212:Tretinoin; D013469:Sulpiride; D017346:Protein Serine-Threonine Kinases; D001058:Apomorphine