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Pigment Cell Melanoma Res. 2018 Nov;31(6):693-707. doi: 10.1111/pcmr.12711. Epub 2018 Jun 5.

Melanocyte development in the mouse tail epidermis requires the Adamts9 metalloproteinase.

Author information

1
Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
2
Department of Oral Biological and Medical Sciences, Faculty of Dentistry, Centre for Blood Research, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
3
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum Munchen, German Research Centre for Environmental Health, Neuherberg, Germany.
4
Chair of Experimental Genetics, School of Life Science, Weihenstephan Technische Universitat, Freising, Germany.
5
German Center for Diabetes Research (DZD), Neuherberg, Germany.
6
Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.

Abstract

The mouse tail has an important role in the study of melanogenesis, because mouse tail skin can be used to model human skin pigmentation. To better understand the development of melanocytes in the mouse tail, we cloned two dominant ENU-generated mutations of the Adamts9 gene, Und3 and Und4, which cause an unpigmented ring of epidermis in the middle of the tail, but do not alter pigmentation in the rest of the mouse. Adamts9 encodes a widely expressed zinc metalloprotease with thrombospondin type 1 repeats with few known substrates. Melanocytes are lost in the Adamts9 mutant tail epidermis at a relatively late stage of development, around E18.5. Studies of our Adamts9 conditional allele suggest that there is a melanocyte cell-autonomous requirement for Adamts9. In addition, we used a proteomics approach, TAILS N-terminomics, to identify new Adamts9 candidate substrates in the extracellular matrix of the skin. The tail phenotype of Adamts9 mutants is strikingly similar to the unpigmented trunk belt in Adamts20 mutants, which suggests a particular requirement for Adamts family activity at certain positions along the anterior-posterior axis.

KEYWORDS:

Adamts; melanoblast development; metalloproteinase; skin pigmentation; tail

PMID:
29781574
DOI:
10.1111/pcmr.12711
[Indexed for MEDLINE]

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