PMID: 12672542Apr 4, 2003

Mouse models of Angelman syndrome, a neurodevelopmental disorder, display different brain regional GABA(A) receptor alterations

Neuroscience Letters
S T SinkkonenE R Korpi


Angelman syndrome is a severe neurodevelopmental disorder with cognitive impairment and neurological deficits. It results from a maternal deletion of human chromosome 15q11-13 containing two candidate genes E6-P ubiquitin-protein ligase (UBE3A) and GABA(A) receptor beta3 subunit (GABRB3), the latter of which has been also linked to autism. To clarify the potential role of GABA(A) beta3 subunit-containing inhibitory receptors in these disorders, we applied ligand autoradiography on brain sections from mice with inactivated GABRB3 or maternal UBE3A genes. Binding of GABA(A) receptor channel ([(35)S]t-butylbicyclophosphorothionate) and benzodiazepine ([(3)H]Ro 15-4513) site ligands was reduced in selected brain regions of the beta3-deficient mice as compared to controls, while the UBE3A-deficient mice failed to show reduced GABA(A) receptors. The results, suggesting two different pathophysiological mechanisms, are in agreement with positron emission tomography results from Angelman syndrome patients of the corresponding genetic backgrounds.


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Related Concepts

BHLHE22 wt Allele
Neurologic Manifestations
Positron-Emission Tomography
Candidate Disease Gene
Gene Deletion Abnormality
GABA-A Receptor
UBE3A gene
Benzodiazepine [EPC]
Plasma Protein Binding Capacity

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Angelman Syndrome

Angelman syndrome is a neurogenetic imprinting disorder caused by loss of the maternally inherited UBE3A gene and is characterized by generalized epilepsy, limited expressive speech, sleep dysfunction, and movement disorders. Here is the latest research.