Skin Diseases in Laboratory Mice: Approaches to Drug Target Identification and Efficacy Screening

Sundberg, John P.; Silva, Kathleen A.; McPhee, Caroline G.; King, Lloyd E.

doi:10.1007/978-1-60761-058-8_12

Cited by 4 publications

(3 citation statements)

References 74 publications

(53 reference statements)

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“…17 Using this method for an adult, female C3H/HeJ mouse, one can see the progressive changes in hair follicle structure, size, and pigmentation (Figs. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. The layers of the skin, most notably the hypodermal fat layer, change in size with the hair cycle.…”

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“…There is a great deal of interest in manipulating the hair cycle with drugs to increase hair growth (such as for androgenetic alopecia) 12 or to stop hair growth altogether. Although performing histopathology is the most definitive way to determine the results of such manipulations, 16 quantifying and mapping changes in hair color, using gray scale estimates to pixel counts with digital morphometric analyses, is an inexpensive and efficient way to quantify efficacy. 18 This simple analysis illustrates the complexity of the skin as a naturally cycling organ.…”

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What Color Is the Skin of a Mouse?

Sundberg

Silva

2011

Vet Pathol

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Laboratory mice naturally come in a large variety of colors ranging from black to white, brown to yellow, and spotted. 10,11 However, as obvious as this feature is, it refers to the color of the mouse's hair, not of its skin. Investigators are perpetually confused when they shave, clip, or chemically depilate mice to see black mice with pink skin or with patches of pink, grey, or black skin. Knowledge of basic physiological differences between mice and humans provides an obvious answer to this extremely commonly asked question. By examining the skin carefully in several inbred strains or the same inbred strain with various coat color mutations, the answer becomes obvious, as do many other peculiarities of the skin commonly overlooked by most investigators ''phenotyping'' mutant mice. One must understand normal anatomy and biology in order to correctly interpret both normal and abnormal features (phenotypes). 8 We present here an evaluation of adults from several different strains with different coat colors to illustrate these important features.Wild-type (normal, þ/þ) retired female breeders from the following inbred strains were used: BALB/cJ (JR#651, albino, white); C3H/HeJ (JR#659, agouti); C57BL/6J (JR#664, black); B6.Cg-Tyr c-J /J (JR#35, white); and DBA/1J (JR#670, dilute brown). All mice were obtained from The Jackson Laboratory (Bar Harbor, ME). Mice were euthanized by CO 2 asphyxiation, shaved with electric clippers (Oster #78005-010, Niles, IL), and photographed on a copy stand with a digital camera. 14 This work was done with our Institutional Animal Care and Use Committee's approval. Skin was removed with a scalpel and cut in a longitudinal, head-to-tail strip, laid flat on aluminum foil, fixed by immersion in Fekete's acid-alcohol-formalin solution overnight, stored in 70% ethanol, trimmed, processed routinely, embedded in paraffin, sectioned at 6 mm, and stained with hematoxylin and eosin. 9,15 Gross photographs of each of these mice illustrate various shades of pink skin with pigmented areas for the colored mice (Figs. 1-5). Next to each gross image is a scanned image of the skin section to correlate histology with the marked anatomic site. Note that hair follicles vary in size, especially in length, which corresponds to the thickness of the hypodermal fat layer. This is the normal hair cycle in the

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What Color Is the Skin of a Mouse?

Sundberg

Silva

2011

Vet Pathol

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“…The truncal pigmentation of rodents is entirely dependent on their follicular melanocytes. Pigment production is active only during the follicle growth (anagen) phase (Park et al 2007; Sundberg et al 2010; Sundberg and Silva 2012). In pigmented mice, rapid hair regrowth after clipping is grossly evident as dark gray/black discoloration of the skin (Figure 5) due to hair follicles entering the anagen phase.…”

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Dermal Toxicity Studies

et al. 2014

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The field of dermal toxicity continues to evolve in order to accurately predict dermal (and systemic) responses in humans to topically applied chemicals. Although the testing methods have undergone extensive refinements, idiosyncrasies and unexpected issues during the conduct of these studies are not unusual due to the plethora of new vehicles available for formulating test substances, changing regulatory requirements, and introducting new strain and/or species of laboratory animals as no single species or method seems to suffice for evaluating skin toxicity. The objective of this article is to illustrate some pragmatic issues that should be considered during the conduct as well as interpretation of dermal toxicity studies. Routine procedure-related issues such as hair clipping, tape stripping, and wrapping the animal's torso to prevent oral ingestion can influence the interpretation. Excipients used in dermal toxicity studies may be nontoxic when used alone but complex dermal formulations can result in unexpected irritation and toxicity. In conclusion, interpretation and risk assessment of dermal toxicity studies should be done in a comprehensive manner, taking into account procedure-related impact on study results, unique species susceptibility, limitation of gross visual (naked eye) observation for evidence of toxicity, and normal anatomical variation.

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Examination of endothelial cell‐induced epidermal regeneration in a mice‐based chimney wound model

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Park

Choi

et al. 2016

Wound Repair Regeneration

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As wound contraction in the cutaneous layer occurs rapidly in mice, mechanical means are typically used to deliberately expose the wound to properly investigate healing by secondary intention. Previously, silicon rings and splinting models were attempted to analyze histological recovery but prevention of surrounding epidermal cell migration and subsequent closure was minimal. Here, we developed an ideal chimney wound model to evaluate epidermal regeneration in murine under hESC-EC transplantation through histological analysis encompassing the three phases of regeneration: migration, proliferation, and remodeling. Human embryonic stem cell derived endothelial cells (hESC-EC) were transplanted due to possessing a well-known therapeutic effect in angiogenesis which also enhances epidermal repair to depict the process of regeneration. Following a standard 1 mm biopsy punch, a chimney manufactured by modifying a 1.7 mL microtube was simply inserted into the excisional wound to complete the modeling process. Under this model, the excisional wound remained fully exposed for 14 days and even after 4 weeks, only a thin transparent layer of epidermal tissue covered the wound site. This approach is able to more accurately depict epidermal repair in relation to histology while also being a user-friendly and cost-effective way to mimic human recovery in rodents and evaluate epithelial repair induced by a form of therapy.

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Skin Diseases in Laboratory Mice: Approaches to Drug Target Identification and Efficacy Screening

Cited by 4 publications

References 74 publications

What Color Is the Skin of a Mouse?

What Color Is the Skin of a Mouse?

Dermal Toxicity Studies

Examination of endothelial cell‐induced epidermal regeneration in a mice‐based chimney wound model

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