Sealed adult mice: new model for enterotoxin evaluation

Area of Science:

• Immunology
• Microbiology
• Genetics

Background:

• Bacterial enterotoxins, such as cholera toxin (CT), induce significant fluid secretion in the gastrointestinal tract.
• Understanding host genetic factors influencing enterotoxin response is crucial for disease management and prevention.

Purpose of the Study:

• To investigate the role of host genetics in mediating responses to cholera enterotoxin and other bacterial enterotoxins.
• To identify specific genetic markers associated with varying levels of susceptibility to enterotoxin-induced fluid secretion.

Main Methods:

• Administered crude cholera enterotoxin (CT) orally to outbred, inbred, and congenic mouse strains converted to sealed adult mice (SAM).
• Assessed fluid secretion by calculating gut weight/body weight ratios at peak response (6 hours post-administration).
• Tested purified enterotoxins from Escherichia coli, Vibrio cholerae, Clostridium difficile, and Vibrio fluvialis, alongside immunization strategies.

Main Results:

• A linear dose-response relationship was observed for CT in experimental mice.
• Various purified enterotoxins and culture filtrates induced significant fluid outpouring.
• Immunization with anti-CT neutralized CT-induced fluid secretion; specific mouse strains (H-2k vs. H-2b haplotypes) exhibited markedly different fluid accumulation ratios, independent of body weight, gut length, age, or sex.

Conclusions:

• Host genetic background, particularly the H-2 haplotype, plays a critical role in determining the susceptibility to enterotoxin-induced intestinal fluid secretion.
• The H-2k haplotype was associated with poor responses, while the H-2b haplotype was linked to good responses to cholera enterotoxin.