Immune Complex Vasculitis with Secondary Ulcerative Dermatitis in Aged C57BL/6NNia Mice

Abstract

A spontaneous, severely pruritic ulcerative dermatitis was initially observed in 33/201 (16.4%) aged C57BL/6NNia mice obtained from the National Institute of Aging. This ulcerative dermatitis also developed in 21/98 (21%) aged C57BL/6 mice in a subsequent experimental group obtained from the same source. The average age of onset in the initial group was 20 months. These animals were negative for ectoparasite infestation and primary bacterial or fungal infection. The lesions varied from acute epidermal excoriation and ulceration to chronic ulceration with marked dermal fibrosis. In the affected animals, leukocytoclastic vasculitis was present in the dermis in both areas of ulceration and areas covered by normal intact epidermis. Immunofluorescent staining of the skin was positive for deposition of IgG, IgM, and fibrinogen in the dermal vessels of the affected mice. Leukocytoclastic vasculitis was not observed in unaffected animals, nor were deposits of immunoglobulin or fibrinogen present in the skin of the control animals. This study provides strong evidence that the ulcerative dermatitis is caused by an immune complex-induced vasculitis. The elucidation of the pathogenesis of this disease is important because of the significant percentage of animals affected and because the C57BL/6 mouse may be a useful model to study human vasculitides.

Practical pathology of aging mice

“…Affected B6 mice are usually pruritic leading to self-mutilation, disease progression and, often, euthanasia for humane reasons. The B6 chronic ulcerative dermatitis has been attributed to many causes (27, 28) most recently primary follicular dystrophy (29). The clinical disease is variable, waxes and wanes, appears to have sex, and season predilections.…”

“…Commonly affected tissues in these studies included the mesentery, tongue heart, reproductive tracts, and kidney. An immune mediate pathogenesis has been proposed (27, 46). In humans with a similar disease processes, polyarteritis nodosa, clinical signs are related to affected organ dysfunction (47).…”

Mouse

“…4.79). Inflammatory changes in the skin may also be secondary to the presence of mites or immune complex-mediated vasculitis (Andrews et al 1994, Frith & Ward 1988. Similar degenerative and inflammatory changes in the ears have been associated with excessive grooming or the presence of metal ear tags (Bell et al 1970, Kitagaki & Hirota 2007.…”

Exploiting the rodent model for studies on the pharmacology of lifespan extension

“…C57BL / 6 mice also tend to exhibit aggression linked to their dominance hierarchy within the cage. This does not usually pose a serious problem, but it can be serious in mice that are suffering from ulcerative dermatitis, a condition in C57BL/ 6 that increases in incidence with age (Andrews et al ., 1994). The aggressive interactions exacerbate the skin problems associated with the ulcerative dermatitis, leading to open wounds that require euthanasia for humane reasons.…”