title: Adam10 haploinsufficiency causes freckle-like macules in Hairless mice.
abstract: The Hairless nuclear receptor co-repressor is required for hair follicle regeneration during the hair cycle. The classical Hairless(Hr) /Hairless(Hr) mouse mutant loses all hair between 2 and 3 weeks of age. As the mice age, their trunk skin develops epidermal pigmentation, a feature of human skin which is not found in normal haired mice. In this report, we present a new, dominant mouse mutation, Pied, which arose within a colony of Hairless(Hr) /Hairless(Hr) mice and causes freckle-like macules on the skin. The Pied macules require Hairless(Hr) homozygosity to form and are composed of localized clusters of epidermal melanocytes. Through linkage analysis, we find that the Pied mutation is a 1914 base pair loss-of-function deletion in the Adam10 zinc metalloprotease gene. The pathways that specifically maintain long-term pigmentation patterns in adults are not well understood. We have identified Adam10 as an inhibitor of melanocyte expansion in adult skin.
authors: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors: Grace
authors: G
authors: Tharmarajah
authors: Laura
authors: L
authors: Faas
authors: Karina
authors: K
authors: Reiss
authors: Paul
authors: P
authors: Saftig
authors: Antony
authors: A
authors: Young
authors: Catherine D
authors: CD
authors: Van Raamsdonk
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002449:Cell Aggregation; D033481:Chromosomes, Mammalian / Q000235:genetics; D017353:Gene Deletion; D057895:Haploinsufficiency / Q000235:genetics*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D017495:Hyperpigmentation / Q000150:complications / Q000235:genetics / Q000473:pathology; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008548:Melanosis / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008812:Mice, Hairless; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012867:Skin / Q000473:pathology; D012880:Skin Pigmentation
chemical_list: D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse