Mouse model implicates GNB3 duplication in a childhood obesity syndrome

Area of Science:

• Genetics
• Neuroscience
• Endocrinology

Background:

• Obesity is a heritable condition and a risk factor for numerous diseases.
• Genomic copy number variation (CNV) is increasingly recognized in early-onset obesity, sometimes with intellectual disability.

Observation:

• A recurrent CNV was identified in a syndrome characterized by intellectual disability, seizures, macrocephaly, and obesity.
• This CNV results in the duplication of over 100 genes on chromosome 12, including the GNB3 gene.

Findings:

• A transgenic mouse model overexpressing GNB3 exhibited significantly higher body weight and increased intraabdominal fat compared to wild-type littermates.
• GNB3 shows high expression in the brain, suggesting a role in satiety and/or metabolism via G-protein signaling.

Implications:

• GNB3 duplication and overexpression are linked to elevated body mass index (BMI).
• This study provides evidence for a genetic syndrome caused by a recurrent CNV involving GNB3, contributing to obesity and intellectual disability.