Table 1.

Summary of the representative preclinical mouse models of human atopic dermatitis

Category	advantages /limitations	Examples	Characteristics	References
Inbred models
	Pros: resembles natural course of human AD; enhanced percutaneous sensitization to haptens and allergens	Flaky tail (ma/ma, Flgft/ft)	Recapitulates barrier defect in a subset of human AD Combined genetic alteration of Flg and Tmem79	(Fallon et al., 2009, Sasaki et al., 2013, Saunders et al., 2013)
	Cons: lack of genetic information in some strains; variable induction protocols when combined with hapten- or allergen-challenges; some models do not spontaneously develop dermatitis under SPF conditions	NC/Nga	Spontaneous onset in conventional housing condition Genetic determinant linked to immune-related genes	(Kohara et al., 2001, Matsuda et al., 1997)
Genetically-engineered models
	Pros: useful in elucidating gene-specific functions in vivo; powerful when crossed with other strains	Overexpression IL-4 (K14-IL4 Tg) IL-13 (K5-tTA-IL13 Tg)	Keratinocyte-specific overexpression of type 2 cytokines recapitulating human AD including chronic parenchymal changes	(Chan et al., 2006, Zheng et al., 2009)
	Cons: time-consuming and expensive to generate; undesirable effect by unexpected gene expression or alteration (i.e. variable penetrance, inefficiency of Cre)	IL-31 (EF1α-IL31 or Eμ-Lck-IL31 Tg)	Pruritus and disruption of the skin barrier	(Dillon et al., 2004)
		TSLP (K5-rtTA-TSLP Tg) IL-18 (K14-IL18 Tg) IL-33 (K14-IL33 Tg)	Keratinocyte expression of type 2 cytokines that activate innate lymphoid cells	(Imai et al., 2013, Konishi et al., 2002, Yoo et al., 2005)
		JAK1 (Jak1spade/spade)	JAK1 hyperactivation leading to barrier dysfunction	(Yasuda et al., 2016)
		Ablation ADAM17 (Adam17fl/fl Sox9Cre)	Spontaneous dysbiosis and eczematous skin inflammation	(Kobayashi et al., 2015)
		CARMA-1 (unmodulated)	N-ethyl-N-nitrosourea-induced, genome-wide mutagenesis model Mutation in mouse ortholog of CARMA-1/CARD11	(Jun et al., 2003)
Induced models by exogenous agents
	Pros: time-controlled induction; applicable to various mouse strains Cons: non-standardized products for some allergens; variable protocols (doses and durations); labor-intensive (daily applications)	Hapten- induced (ex. oxazolone, TNCB) Allergen-induced (ex. ovalbumin, house dust mite)	AD-like inflammation induced by repeated challenge Ambiguous distinction between AD and allergic contact dermatitis	(Kitagaki et al., 1995, Kitagaki et al., 1997, Matsuoka et al., 2003, Spergel et al., 1998, Wang et al., 2007)
		MC903 (calcipotriol)- induced	High reproducibility of AD-like responses in various strains	(Kim et al., 2013, Li et al., 2006, Myles et al., 2016, Naidoo et al., 2018, Oetjen et al., 2017)