Rhino Mouse Acne model

Overview

Introduction

Rhino mouse acne model has been useful in assessing the comedolytic activity of drugs/compounds (i.e. retinoids)

Phenotype Hr^rh/Hr^rh is due to an autosomal recessive mutation in the hairless (hr) gene

In Rhino mice, utriculi are derived from the infundibular zone of the initial follicular units, and are histologically similar to comedones

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Protocol summary

Rhino mouse strain animals with application of compounds / new drugs on back skin

Histology evaluation on skin of utriculi (principal efficacy endpoint)

Evaluation of in vivo / ex vivo / analysis as secondary efficacy endpoints

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Typical results

Typical results obtained with this model are presented below:

Evaluation	Parameter	Group control (excipient / topical)	Test group (retinoid / topical)
*In vivo*	Bodyweight	NE (No Effect)	NE or decrease
	Back skin scaling (visual scoring)	NE	Slight increase (dry skin appearance)
	Back skin erythema (visual scoring)	NE	Increase (irritation)
	Back skin thickness (calipering)	NE	NE or increase
	Epidermis thickness (OCT / Optical Coherence Tomography)
*Ex vivo* (histology)	HES (Overview)
	Utriculi	NE	Very important decrease (-80 to -90%)
	Sebaceous glands	NE	NE on short periods of treatment
	Epidermis thickness	NE	Increase (epidermal hyperplasia)
	Dermis inflammation	NE	Increase (local inflammation slight to moderate)

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Rhino Mouse Acne model / Detailed protocol

Mutant strain RHJ/LeJ Homozygous for Hr^rh-J / JAX stock #001591

Age: Supplier dependent (generally from 8 to 12 weeks)

Gender: M and/or F / Supplier dependent

Randomization on age + gender at reception

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Application of dermatological pharmaceutical products

Ready to use formulations / Formulation screening on request

Intra-dermal route (i.e. Medical Devices or injectable drugs)

Topical route / Reference drugs: Isotretinoin or Adapalene or Bexarotene

Oral route / Reference drug: Isotretinoin

Treatment duration: 2-3 weeks

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Evaluation of clinical macroscopic signs

Body weight / General behavior

Skin thickness / Caliper (back skin)

Skin macroscopic description (back skin):

Scaling (skin dryness)

Erythema (skin redness)

Other macroscopic skin observations

Sebum production using sebumeter

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In vivo imaging

Macroscopical observation: Digital pictures of back skin

Sub-macroscopical exploration: Optical Coherence Tomography (OCT) for epidermis thickness measurement

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Ex vivo imaging

Histology on back skin slices obtained from paraffin blocks or frozen blocks

HES (Hemalun-Eosin-Safran) / Overall evaluation of efficacy (utriculi / sebaceous glands)

Immuno-histochemistry

Ki67 staining for keratinocyte / fibroblast / sebocyte proliferation index calculation

Other stainings on request

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Other ex vivo imaging techniques of interest:

3D reconstruction of sebaceous glands for volume evaluation

Light Sheet microscopy (in collaboration)

MALDI imaging (in collaboration)

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Samples collection and analysis

Plasma and skin sampling, sebum sampling (surface skin lipids (SSLs) analysis)

Cytokines analysis in skin extract / plasma (terminal sampling))

– Single ELISA assay (1-2 cytokines)

– Multiplexed analysis of cytokines (>2 cytokines)

Sebum lipidomics collected in vivo (repeated sampling) or at termination for evaluation sebum composition:

– Fatty acids

– Sterols

– Cholesterol

– Wax esters

– Triglycerides

– Cholesteryl esters

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Rhino Mouse Acne model / Conclusion

Rhino mouse model is a first intention model, fast and reproducible.

6 animals per group are generally sufficient to underline anti-acne effect of new therapeutics (based on difference of at least 20 to 30% of utriculi surface).

This model is well adapted for anti-seborrheic new drugs testing.

Cautions to be taken on this model :

Use of previously untested excipients should be avoid as they could cause false positive, false negative or local irritation

Formulation physico-chemistry must be well known (pH, osmolarity, etc…)

Drug pharmacokinetics / ADME / transcutaneous passage should be known to optimize dosing

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Do not hesitate to contact us if you need more information or a quotation on this model.

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Bibliography of interest

Seiberg, M., et al. The effects of trypsin on apoptosis, utriculi size, and skin elasticity in the Rhino mouse. J. Invest. Dermatol. 109, 370–376 (1997).
Hsia, E., et al. Effects of topically applied acitretin in reconstructed human epidermis and the rhino mouse. J. Invest. Dermatol. 128, 125–30 (2008).
Benavides, F., et al. The hairless mouse in skin research. J. Dermatol. Sci. 53, 10–18 (2009).
Nieves, N. J., et al. Identification of a unique subset of 2-methylene-19-nor analogs of vitamin D with comedolytic activity in the rhino mouse. J. Invest. Dermatol. 130, 2359–67 (2010).