Related Experiment Video
Updated: May 6, 2026
07:44
Localization of the Locus Coeruleus in the Mouse Brain
Published on: March 7, 2019
18.0K
Atp7b-dependent choroid plexus dysfunction causes transient copper deficit and metabolic changes in the developing
Clorissa L Washington-Hughes1, Shubhrajit Roy1, Herana Kamal Seneviratne2
1Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Plos Genetics
|January 10, 2023
Summary
Copper transporter Atp7b is crucial for brain development, maintaining choroid plexus structure and function. Its absence causes copper deficiency, impacting brain metabolism and potentially exacerbating chelation therapy side effects.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Copper (Cu) is vital for brain development and function.
- Atp7a and Atp7b are key Cu transporters maintaining homeostasis.
- The specific role of Atp7b in the developing brain was unclear.
Purpose of the Study:
- To elucidate the role of Atp7b in postnatal brain development.
- To investigate the impact of Atp7b deficiency on choroid plexus (ChPl) morphology and function.
- To identify metabolic consequences of Atp7b inactivation.
Main Methods:
- Inactivation of the Atp7b gene in a mouse model.
- Analysis of ChPl morphology, cytoskeleton, and cell-cell contacts.
- Assessment of Cu transporter localization (Atp7a, Slc31a1) and brain Cu levels.
- Analysis of catecholamine levels and brain lipidome.
Main Results:
- Atp7b deficiency disrupts ChPl structure, microvilli, and cilia.
- Loss of apical Slc31a1 and intracellular Atp7a upregulation in ChPl.
- Significant brain copper deficit in young animals, improving with age.
- Downregulation of Atp7a in locus coeruleus, catecholamine imbalance, and altered brain lipidome.
Conclusions:
- Atp7b plays a critical role in developing brain's choroid plexus.
- Atp7b deficiency leads to copper deficit and metabolic changes.
- Findings highlight potential risks of Cu chelation therapy in certain contexts.
