Developmental and foliation changes due to dysregulation of adenosine kinase in the cerebellum.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
14 11 2023
14 11 2023
Historique:
received:
10
07
2023
accepted:
09
11
2023
medline:
16
11
2023
pubmed:
15
11
2023
entrez:
14
11
2023
Statut:
epublish
Résumé
Adenosine kinase (ADK), the major adenosine-metabolizing enzyme, plays a key role in brain development and disease. In humans, mutations in the Adk gene have been linked to developmental delay, stunted growth, and intellectual disability. To better understand the role of ADK in brain development, it is important to dissect the specific roles of the two isoforms of the enzyme expressed in the cytoplasm (ADK-S) and cell nucleus (ADK-L). We, therefore, studied brain development in Adk-tg transgenic mice, which only express ADK-S in the absence of ADK-L throughout development. In the mutant animals, we found a reduction in the overall brain, body size, and weight during fetal and postnatal development. As a major developmental abnormality, we found a profound change in the foliation pattern of the cerebellum. Strikingly, our results indicated aberrant Purkinje cells arborization at P9 and accelerated cell death at P6 and P9. We found defects in cerebellar cell proliferation and migration using a bromodeoxyuridine (BrdU)-based cell proliferation assay at postnatal day 7. Our data demonstrate that dysregulation of ADK expression during brain development profoundly affects brain growth and differentiation.
Identifiants
pubmed: 37963945
doi: 10.1038/s41598-023-47098-5
pii: 10.1038/s41598-023-47098-5
pmc: PMC10645999
doi:
Substances chimiques
Adenosine Kinase
EC 2.7.1.20
Protein Isoforms
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
19831Informations de copyright
© 2023. The Author(s).
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