A candidate gene for the mouse mutation tubby

Area of Science:

• Genetics
• Molecular Biology
• Obesity Research

Background:

• The tubby mouse model exhibits late-onset obesity, insulin resistance, and sensory deficits, closely resembling human obesity syndromes like Alström and Bardet-Biedl.
• Unlike rapid juvenile-onset obesity in db and ob mice, tubby mouse obesity develops gradually, making it a relevant model for human late-onset obesity.

Purpose of the Study:

• To identify the genetic cause of the tubby phenotype.
• To elucidate the molecular mechanism underlying the observed obesity and sensory deficits.

Main Methods:

• Genetic analysis to identify mutations in the tub gene.
• Transcriptional analysis to characterize altered mRNA and protein products.
• Comparison of gene expression levels in tubby mice versus control (B6) mice.

Main Results:

• A G --> T transversion mutation in the tub gene was identified, disrupting a splice site.
• The mutation results in altered transcripts, including a larger transcript with an unspliced intron and a prematurely truncated transcript.
• Tubby mice show increased brain mRNA levels and potential cellular apoptosis linked to the mutated tub gene expression.

Conclusions:

• The identified tub gene mutation is the cause of the multifaceted tubby phenotype.
• The molecular alterations provide insight into the pathogenesis of obesity and sensory deficits.
• The tubby mouse model offers a valuable platform for studying human obesity syndromes and developing therapeutic strategies.