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PMID:21949658

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Citation

Hellström, AR, Watt, B, Fard, SS, Tenza, D, Mannström, P, Narfström, K, Ekesten, B, Ito, S, Wakamatsu, K, Larsson, J, Ulfendahl, M, Kullander, K, Raposo, G, Kerje, S, Hallböök, F, Marks, MS and Andersson, L (2011) Inactivation of Pmel alters melanosome shape but has only a subtle effect on visible pigmentation. PLoS Genet. 7:e1002285

Abstract

PMEL is an amyloidogenic protein that appears to be exclusively expressed in pigment cells and forms intralumenal fibrils within early stage melanosomes upon which eumelanins deposit in later stages. PMEL is well conserved among vertebrates, and allelic variants in several species are associated with reduced levels of eumelanin in epidermal tissues. However, in most of these cases it is not clear whether the allelic variants reflect gain-of-function or loss-of-function, and no complete PMEL loss-of-function has been reported in a mammal. Here, we have created a mouse line in which the Pmel gene has been inactivated (Pmel⁻/⁻). These mice are fully viable, fertile, and display no obvious developmental defects. Melanosomes within Pmel⁻/⁻ melanocytes are spherical in contrast to the oblong shape present in wild-type animals. This feature was documented in primary cultures of skin-derived melanocytes as well as in retinal pigment epithelium cells and in uveal melanocytes. Inactivation of Pmel has only a mild effect on the coat color phenotype in four different genetic backgrounds, with the clearest effect in mice also carrying the brown/Tyrp1 mutation. This phenotype, which is similar to that observed with the spontaneous silver mutation in mice, strongly suggests that other previously described alleles in vertebrates with more striking effects on pigmentation are dominant-negative mutations. Despite a mild effect on visible pigmentation, inactivation of Pmel led to a substantial reduction in eumelanin content in hair, which demonstrates that PMEL has a critical role for maintaining efficient epidermal pigmentation.

Links

PubMed PMC3174228 Online version:10.1371/journal.pgen.1002285

Keywords

Alleles; Animals; Cells, Cultured; Epidermis/cytology; Epidermis/metabolism; Hair Color/genetics; HeLa Cells; Humans; Melanins/biosynthesis; Melanins/genetics; Melanosomes/metabolism; Melanosomes/ultrastructure; Membrane Glycoproteins/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron; Mutation; Oxidoreductases/metabolism; Phenotype; Pigmentation/genetics; Skin/metabolism; gp100 Melanoma Antigen/genetics; gp100 Melanoma Antigen/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PMEL

involved_in

GO:0048023: positive regulation of melanin biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PMEL

GO:0048023: positive regulation of melanin biosynthetic process

ECO:0000315:

P

Based on results in Table 1

complete
CACAO 2277

MOUSE:ASIP

involved_in

GO:0048023: positive regulation of melanin biosynthetic process

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P07147
UniProtKB:Q60696

P

Seeded From UniProt

complete

MOUSE:ASIP

GO:0048023: positive regulation of melanin biosynthetic process

ECO:0000316:

UniProtKB:P07147 UniProtKB:Q60696


P

Based on results in Table 2

complete
CACAO 2279

MOUSE:TYRP1

GO:0048023: positive regulation of melanin biosynthetic process

ECO:0000316:

UniProtKB:Q03288 UniProtKB:Q60696


P

Based on results in Table 2

complete
CACAO 2280

MOUSE:TYRP1

involved_in

GO:0048023: positive regulation of melanin biosynthetic process

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q03288
UniProtKB:Q60696

P

Seeded From UniProt

complete


See also

References

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