Hairless Mice

After Melish and Glasgow reported that an experimental infection resembling the scalded-skin syndrome in humans could be produced by certain strains of Staphylococcus aureus in neonatal mice (3) and after the subsequent demonstration that this response was mediated by a soluble protein called exfoliatin (2), it was recognized that Swiss mice became refractory to this toxin about 5 days after birth when hair development was obvious (1-4). Whereas 2 to 3 median effective doses (ED50) of exfoliatin caused generalized exfoliation and death in neonatal mice, doses as high as 1,200 EDW0 given older mice (with hair) caused no skin loss. One ED50 was defined as that amount of exfoliatin which, when inoculated subcutaneously into 1-day-old Swiss mice, caused a positive Nikolsky sign in 50% of animals in 3 hr (2). Much higher doses (4,000 to 8,000 ED5o) could elicit a positive Nikolsky sign on the footpads, ears, or tail, but did not cause a generalized response (2). Because resistance to exfoliatin could either be related to hair production or be dependent upon other mechanisms occurring concurrently at this age, the response of hairless mutant mice to exfoliatin was studied. In neonatal mice, exfoliatin causes extensive skin involvement, and death presumably results from loss of fluid and electrolytes through the denuded regions. Whether this is the sole mechanism of lethality, or even an actual one, is not known. Therefore, any subsequent reference to deaths should be interpreted cautiously with this in mind. Differences in mortality between young and old animals are mentioned simply for comparisdn and could reflect differences in such factors as the (i) amount of skin loss, (ii) ability to cope with dehydration, (iii) susceptibility to other possible activities of exfoliatin, or (iv) susceptibility to unrecognized products produced by the living organisms or present in exfoliatin preparations. Thus, the purpose of this report is to describe primarily the effects of exfoliatin in the skin of animals undergoing study. A breeding stock of hairless mutant mice (HRS/J), consisting of heterozygous females and homozygous males, was obtained from The Jackson Lab, Bar Harbor, Me. Homozygous offspring produced hair as usual (by day 5) and developed a full coat; however, this coat was subsequently lost, and at the age of one month these mice were again hairless. Heterozygotes developed and maintained a hair coat indistinguishable from that of normal mice. Exfoliatin was produced, partially purified, and assayed as previously described (2). Traces of contaminating alpha toxin were neutralized by the addition to the inoculum of small quantities (1 unit/ml) of staphylococcal antitoxin (Connaught Labs, Toronto). This antitoxin did not contain antibody to exfoliatin (2). While they possessed hair, homozygous mutant mice were resistant to 500 ED50 of exfoliatin given subcutaneously. Upon loss of their coat they again responded to exfoliatin with localized exfoliation around the site of inoculation, but were decidedly more resistant than neonatal mice, as judged by the amount of skin involved and survival of doses of 500 ED50 (Fig. 1). Animals given 1,000 EDw succumbed 2 to 5 days after inoculation. Mutant mice given 500 ED50 of exfoliatin while hair loss was just beginning (on the head) developed a positive Nikolsky sign on the hairless regions, but no actual exfoliation there or elsewhere. Sibling heterozygotes did not react to these doses of exfoliatin. Hairless homozygotes inoculated subcutaneously with 5 x 108 washed S. aureus strain TG (2, 3) experienced exfoliative lesions which, although patchy in nature, were widely distributed over the body (Fig. 2). About one-half of these