Journal
SCIENTIFIC REPORTS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-023-47098-5
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Adenosine kinase (ADK), a crucial enzyme in adenosine metabolism, is involved in brain development and diseases. Mutations in the Adk gene are associated with developmental delay, stunted growth, and intellectual disability in humans. Study on transgenic mice expressing only ADK-S revealed that dysregulation of ADK expression during brain development profoundly affects brain growth and differentiation, leading to cerebellar abnormalities and accelerated cell death.
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.
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