Dataset Information

Immune responses in a mouse model of vitiligo with spontaneous epidermal de- and repigmentation.

ABSTRACT: To generate a mouse model of spontaneous epidermal depigmentation, parental h3TA2 mice, expressing both a human-derived, tyrosinase-reactive T-cell receptor on T cells and the matching HLA-A2 transgene, were crossed to keratin 14-promoter driven, stem cell factor transgenic (K14-SCF) mice with intra-epidermal melanocytes. In resulting Vitesse mice, spontaneous skin depigmentation precedes symmetrical and sharply demarcated patches of graying hair. Whereas the SCF transgene alone dictates a greater retinoic acid receptor-related orphan receptor gamma (ROR?t)(+) T-cell compartment, these cells displayed markedly increased IL-17 expression within Vitesse mice. Similar to patient skin, regulatory T cells were less abundant compared with K14-SCF mice, with the exception of gradually appearing patches of repigmenting skin. The subtle repigmentation observed likely reflects resilient melanocytes that coexist with skin-infiltrating, melanocyte-reactive T cells. Similar repigmenting lesions were found in a different TCR transgenic model of vitiligo developed on an SCF transgenic background, supporting a role for SCF in repigmentation.

SUBMITTER: Eby JM

PROVIDER: S-EPMC4470702 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Immune responses in a mouse model of vitiligo with spontaneous epidermal de- and repigmentation.

Eby Jonathan M JM Kang Hee-Kap HK Klarquist Jared J Chatterjee Shilpak S Mosenson Jeffrey A JA Nishimura Michael I MI Garrett-Mayer Elizabeth E Longley B Jack BJ Engelhard Victor H VH Mehrotra Shikhar S Le Poole I Caroline IC

Pigment cell & melanoma research 20140721 6

To generate a mouse model of spontaneous epidermal depigmentation, parental h3TA2 mice, expressing both a human-derived, tyrosinase-reactive T-cell receptor on T cells and the matching HLA-A2 transgene, were crossed to keratin 14-promoter driven, stem cell factor transgenic (K14-SCF) mice with intra-epidermal melanocytes. In resulting Vitesse mice, spontaneous skin depigmentation precedes symmetrical and sharply demarcated patches of graying hair. Whereas the SCF transgene alone dictates a great ...[more]

PMID: 24935676

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Project description:To develop a translational mouse model for the study and measurement of non-evoked pain in the orofacial region by establishing markers of nociceptive-specific grooming behaviors in the mouse.Some of the most prevalent and debilitating conditions involve pain in the trigeminal distribution. Although there are current therapies for these pain conditions, for many patients, they are far from optimal. Understanding the pathophysiology of pain disorders arising from structures innervated by the trigeminal nerve is still limited, and most animal behavioral models focus on the measurement of evoked pain. In patients, spontaneous (non-evoked) pain responses provide a more accurate representation of the pain experience than do responses that are evoked by an artificial stimulus. Therefore, the development of animal models that measure spontaneous nociceptive behaviors may provide a significant translational tool for a better understanding of pain neurobiology.C57BL/6 mice received either an injection of 0.9% saline solution or complete Freund's adjuvant into the right masseter muscle. Animals were video-recorded and then analyzed by an observer blind to the experiment group. The duration of different facial grooming patterns performed in the area of injection were measured. After 2 hours, mice were euthanized and perfused, and the brainstem was removed. Fos protein expression in the trigeminal nucleus caudalis was quantified using immunohistochemistry to investigate nociceptive-specific neuronal activation. A separate group of animals was treated with morphine sulfate to determine the nociceptive-specific nature of their behaviors.We characterized and quantified 3 distinct patterns of acute grooming behaviors: forepaw rubbing, lower lip skin/cheek rubbing against enclosure floor, and hindpaw scratching. These behaviors occurred with a reproducible frequency and time course, and were inhibited by the analgesic morphine. Complete Freund's adjuvant-injected animals also showed Fos labeling consistent with neuronal activation in nociceptive-specific pathways of the trigeminal nucleus after 2 hours.These behaviors and their correlated cellular responses represent a model of trigeminal pain that can be used to better understand basic mechanisms of orofacial pain and identify new therapeutic approaches to this common and challenging condition.

Dataset Information

Immune responses in a mouse model of vitiligo with spontaneous epidermal de- and repigmentation.

Publications

Immune responses in a mouse model of vitiligo with spontaneous epidermal de- and repigmentation.

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