Ann Dermatol.  2015 Jun;27(3):257-264. 10.5021/ad.2015.27.3.257.

HR-1 Mice: A New Inflammatory Acne Mouse Model

• Jang YH
• Lee KC
• Lee SJ
• Kim DW
• Lee WJ

• KMID: 2352495
• DOI: http://doi.org/10.5021/ad.2015.27.3.257

Abstract

BACKGROUND
There is no appropriate in vivo animal model that reflects the inflammatory response of human acne.
OBJECTIVE
This study investigated the effect of Propionibacterium acnes on the development of inflammatory acne-like lesions in four mouse strains with different degrees of immune response for the development of an optimal mouse model of inflammatory acne.
METHODS
Human P. acnes suspensions (10(8) and 10(9) colony forming unit [CFU]/microl) were injected into the backs of HR-1, BALB/c, vitamin D receptor-knockout (VDR k/o), and severe combined immunodeficiency disease mice. Inflammation levels were evaluated two weeks after injection of P. acnes suspensions. In addition, histopathological examination and immunohistochemical staining of the expressions of inflammatory biomarkers (i.e., CD4+/CD8+ T lymphocytes, neutrophils, myeloperoxidase, interleukin-1beta, matrix metalloprotease (MMP)-2, MMP-3, MMP-9, toll-like receptor (TLR)-2, LL-37, and integrin alpha6) were performed on tissue specimens.
RESULTS
The HR-1 mouse strain exhibited the most remarkable inflammatory reaction with epithelial proliferation and microcomedone-like cyst formation. HR-1 mice also demonstrated aberrant integrin expression in the epidermis around both inflamed lesions and newly formed microcomedones. These findings were more prominent in the group receiving 10(9) CFU/microl P. acnes than 10(8) CFU/microl. MMP-9 expression in HR-1 mice was also upregulated around the microcomedone-like cysts. Finally, expression levels of TLR-2 and LL-37 were higher in HR-1 and BALB/c mice than the VDR k/o and SCID mice strains.
CONCLUSION
P. acnes induces acneiform inflammation with small microcomedones in HR-1 mice. Therefore, the HR-1 mouse strain represents a good candidate for the development of a new inflammatory acne mouse model.

Keyword

Acne vulgaris; Animal model; Inflammation; Propionibacterium acnes

MeSH Terms

Acne Vulgaris*
Animals
Biomarkers
Epidermis
Humans
Inflammation
Interleukin-1beta
Mice*
Mice, SCID
Models, Animal
Neutrophils
Peroxidase
Propionibacterium acnes
Severe Combined Immunodeficiency
Stem Cells
Suspensions
T-Lymphocytes
Toll-Like Receptors
Vitamin D
Interleukin-1beta
Peroxidase
Suspensions
Toll-Like Receptors
Vitamin D

Figure

• 

  Fig. 1 Two weeks after injection with 108 colony forming unit/µl Propionibacterium acnes suspension, clinical inflammation was significantly more prominent of HR-1 mice than the three other strains. The extent of inflammation tended to be proportional to the concentration of injected P. acnes. VDR k/o: vitamin D receptor-knockout mice, SCID: severe combined immunodeficiency mice.

• 

  Fig. 2 Injected HR-1 mice exhibited significantly greater epidermal thickening than BALB/c mice. The degree of epidermal thickening was also dependent on the concentration of injected Propionibacterium acnes. CFU: colony forming unit.

• 

  Fig. 3 Injected HR-1 mice exhibited several microcomedone-like cysts around the inflammatory focus induced by Propionibacterium acnes injection. CFU: colony forming unit.

• 

  Fig. 4 Integrin α6 expression was significantly higher in the lower epidermis of injected HR-1 mice (particularly at 109 CFU/µl) than the other three mouse strains (staining method: H&E). CFU: colony forming unit, VDR k/o: vitamin D receptor-knockout mice, SCID: severe combined immunodeficiency mice.

• 

  Fig. 5 Injected HR-1 and BALB/c mice exhibited higher toll-like receptor-2 expression in the epidermis than VDR k/o and SCID mice (staining method: H&E). CFU: colony forming unit, VDR k/o: vitamin D receptor-knockout mice, SCID: severe combined immunodeficiency mice.

• 

  Fig. 6 Matrix metalloprotease-9 expression was significantly higher in the dermis of injected HR-1 mice than the other three strains; expression was more prominent around microcomedone-like cysts (staining method: H&E). CFU: colony forming unit, VDR k/o: vitamin D receptor-knockout mice, SCID: severe combined immunodeficiency mice.

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