Demodex musculi Infestation in Genetically Immunomodulated Mice

Abstract

Demodex musculi, a prostigmatid mite that has been reported infrequently in laboratory mice, has been identified with increasing frequency in contemporary colonies of immunodeficient mice. Here we describe 2 episodes of D. musculi infestation with associated clinical signs in various genetically engineered mouse strains, as well as treatment strategies and an investigation into transmissibility and host susceptibility. The first case involved D. musculi associated with clinical signs and pathologic lesions in BALB/c-Tg(DO11.10)Il13(tm) mice, which have a defect in type 2 helper T cell (Th2) immunity. Subsequent investigation revealed mite transmission to both parental strains (BALB/c-Tg[DO11.10] and BALB/c-Il13(tm)), BALB/c-Il13/Il4(tm), and wild-type BALB/c. All Tg(DO11.10)Il13(tm) mice remained infested throughout the investigation, and D. musculi were recovered from all strains when they were cohoused with BALB/c-Tg(DO11.10)Il13(tm) index mice. However, only Il13(tm) and Il13/Il4(tm) mice demonstrated persistent infestation after index mice were removed. Only BALB/c-Tg(DO11.10)Il13(tm) showed clinical signs, suggesting that the phenotypic dysfunction of Th2 immunity is sufficient for persistent infestation, whereas clinical disease associated with D. musculi appears to be genotype-specific. This pattern was further exemplified in the second case, which involved NOD.Cg-Prkdc(scid)Il2r(tm1Wjl)/SzJ (NSG) and C;129S4 Rag2(tm1.1Flv) Il2rg(tm1.1Flv)/J mice with varying degrees of blepharitis, conjunctivitis, and facial pruritis. Topical amitraz decreased mite burden but did not eliminate infestation or markedly ameliorate clinical signs. Furthermore, mite burden began to increase by 1 mo posttreatment, suggesting that topical amitraz is an ineffective treatment for D. musculi. These experiences illustrate the need for vigilance regarding opportunistic and uncommon pathogens in rodent colonies, especially among mice with immunologic deficits.

Figure 1.

Gross and histologic findings in BALB/c-Tg(DO11.10)IL13^tm mice. (A and B). Gross lesions associated with Demodex musculi infestation in BALB/c-Tg(DO11.10)IL13^tm mice. (A) Alopecia and excoriations in the dorsal cervical, intrascapular and periocular regions (arrows). (B) Facial alopecia and severe excoriation of the external ear canals and perioccular regions (arrows). (C) Hair plucks from affected mice. Hair plucks were taken from the head and dorsal cervical region of Tg(DO11.10)IL13^tm mice, placed on a slide with mineral oil, and examined by light microscopy. The size and morphology of the mites identified in these samples are consistent with Demodex musculi (arrow). Bar, 20 μm. (D through F). Photomicrographs of skin sections from BALB/c-Tg(DO11.10)IL13^tm mice infested with Demodex musculi. Sections of mites were present within dilated hair follicles (arrows, panels D and E; black asterisk, panel F) and sebaceous glands (arrow, panel F). Mite infestation was accompanied by epidermal hyperplasia with superficial erosions and cellular crusts (white asterisk, panel E). Superficial periadnexal inflammation was evident (white asterisk, panel F). Bar: 50 μm (D), 100 μm (E, F)

Figure 2.

Gross and histologic findings in NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ (NSG) and C;129S4-Rag2^tm1.1Flv Il2rg^tm1.1Flv/J mice. (A and B) Affected mice had variable degrees of (A) dorsal hypotrichosis, scaling, and erythema and (B) accompanied by blepharitis. (C) Fur plucks revealed an arthropod with the elongated abdominal morphology consistent with Demodex musculi . Mineral oil mount; Bar, 20 μm. (D) Histopathology of the dorsal interscapular region revealed mites within follicles. In many infested follicles, inflammation was minimal to absent. Hematoxylin and eosin stain; bar, 50 μm.

Figure 3.

Mite burden at baseline, after the second bath, and at 2 and 4 wk after the final (that is, 4th) treatment with amitraz. Mite numbers declined in response to amitraz but started to return to pretreatment levels after discontinuation.