Sealed adult mice: new model for enterotoxin evaluation

Abstract

Outbred, inbred, and congenic strains of conventional mice which were ano-rectally occluded with cyanoacrylate ester glue and converted to sealed adult mice (SAM) were given, per os, crude cholera enterotoxin (CT) in 10% NaHCO3. At 6 h when the response was maximal, mice were killed, the small intestines were removed, and gut weight/body weight ratios were calculated. Experimental mice gave a linear response after receiving 1.5 to 60 micrograms of CT. Purified heat-stable enterotoxin from Escherichia coli and purified heat-labile enterotoxins from E. coli, Vibrio cholerae, and Clostridium difficile all elicited vigorous fluid outpouring as did culture filtrates from Vibrio fluvialis with cytotoxic activity. Active and passive immunization with crude CT completely or partially neutralized fluid secretion due to CT. Monospecific anti-CT incubated with CT before feeding also eliminated the response. Mice pretreated with penicillin, held in barrier cages, converted to SAM, and fed live vibrios, showed fluid responses similar to those seen with low doses of CT. Each of six different strains of inbred mice fed a half-maximal fluid accumulation response dose of CT gave fluid accumulation ratios which varied fourfold. There was no correlation of fluid accumulation with body weight, gut length, age, or sex. All poor responders were of H-2k haplotype and all good responders were H-2b. BALB congenic mice which differed only in H-2 haplotypes showed the same correlations, and body weights and gut lengths of all haplotypes were not significantly different.