Clostridial enteropathy in lactating outbred swiss-derived (ICR) mice.

suspected in these mouse outbreaks but has not been isolated from affected mice. The present report describes a severe, necrotizing enterocolitis associated with overgrowth of C. perfringens type A in lactating Swiss-derived (ND4) mice. Mice nursing large litters of pups in the second week of life were the most severely affected. The organism isolated from dead or moribund mice was positive by polymerase chain reaction assay for the gene for the C. perfringens B toxin, but actual toxin production was not determined. The disease in this mouse colony was ameliorated by increasing the fat and calorie content of the diet of lactating dams, which each received 1 g peanut butter every 48 h. A disease of unknown etiology associated with bloating, failure of lactation, and unexpected death in mice has been re- ported sporadically in multiple countries. 11,16 The most complete description of the syndrome described an outbreak involving 50 mice of various strains that died or were euthanized over a period of 2 y. 11 An outbreak of similar disease was described in 30 female SAM-P/6 mice. 16 The cause of the de!cient lactation syndrome was not identi! ed in either report, but enterotoxemia due to clostridial infection or overgrowth was suspected in both instances. 11,16 Previous reports have focused on the lesions in the most severely affected animals; however, the present report shows that clostridial overgrowth in mice can be severe or sub- clinical and can interfere with productivity and experimental variables. This report is unique because of the organisms that were identi! ed, the link with lactational insuf! ciency, and treat- ment of the population with nutritional supplementation. Clostridial organisms, especially the various serotypes of Clostridium perfringens, have long been recognized as a cause of enteritis and enterotoxemia in a variety of species. C. perfringens type A enterotoxemia is an important cause of food-born illness in people. 15 Enterotoxemia caused by C. perfringens types B, C, and D is a common cause of morbidity and mortality in piglets, calves, and lambs. C. perfringens type D is associated with a syn- drome in ruminants, particularly sheep, known as 'overeating disease' or 'pulpy kidney disease.' The disease is most fre- quently identi! ed in sheep fed high-calorie, high-carbohydrate feedlot rations or who are nursing older twin lambs. 1,14 There have been few published reports of clostridial enteric disease in mice. 3,13,17 One early report described enterotoxemia associated with C. perfringens type D in caesarean-derived, bar- rier-sustained suckling mice. 3 A report of necrotizing enteritis in young RFM/M mice characterized the C. perfringens organ- ism as simply 'non-type-A' because of lack of comparative antisera. 13 C. perfringens types B and D were isolated from the gastrointestinal tracts of adult, germ-free BALB/c mice with enterotoxemia. Some of these mice also had left atrial enlarge- ment with thrombus formation, and C. perfringens type B was isolated from the left atria. 17 Here we describe an epizootic of necrohemorrhagic enteritis, lactational insuf! ciency, and bloat- ing associated with clostridial overgrowth in a population of outbred mice. Included in this report are the clinical signs in the affected mice, the effect of the disease on the behavior of the affected dams and their pups, necropsy !ndings, and results of microbiologic investigation.