Inactivation of Pmel Alters Melanosome Shape But Has Only a Subtle Effect on Visible Pigmentation
Publication Date
September 15, 2011
Journal
PLOS Genetics
Authors
Anders R. Hellström, Brenda Watt, Shahrzad Shirazi Fard, Danièle Tenza, et al
Volume
7
Issue
9
Pages
e1002285
DOI
https://dx.plos.org/10.1371/journal.pgen.1002285
Publisher URL
http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1002285
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/21949658
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174228
Europe PMC
http://europepmc.org/abstract/MED/21949658
Web of Science
000295419100034
Scopus
80053436599
Mendeley
http://www.mendeley.com/research/inactivation-pmel-alters-melanosome-shape-only-subtle-effect-visible-pigmentation
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Mendeley | Further Information

{"title"=>"Inactivation of PMEL alters melanosome shape but has only a subtle effect on visible pigmentation", "type"=>"journal", "authors"=>[{"first_name"=>"Anders R.", "last_name"=>"Hellström", "scopus_author_id"=>"14028196400"}, {"first_name"=>"Brenda", "last_name"=>"Watt", "scopus_author_id"=>"35083004400"}, {"first_name"=>"Shahrzad Shirazi", "last_name"=>"Fard", "scopus_author_id"=>"37002128700"}, {"first_name"=>"Danièle", "last_name"=>"Tenza", "scopus_author_id"=>"6603794950"}, {"first_name"=>"Paula", "last_name"=>"Mannström", "scopus_author_id"=>"6507155155"}, {"first_name"=>"Kristina", "last_name"=>"Narfström", "scopus_author_id"=>"7003710840"}, {"first_name"=>"Björn", "last_name"=>"Ekesten", "scopus_author_id"=>"55979805200"}, {"first_name"=>"Shosuke", "last_name"=>"Ito", "scopus_author_id"=>"7404826072"}, {"first_name"=>"Kazumasa", "last_name"=>"Wakamatsu", "scopus_author_id"=>"7102008426"}, {"first_name"=>"Jimmy", "last_name"=>"Larsson", "scopus_author_id"=>"7201729954"}, {"first_name"=>"Mats", "last_name"=>"Ulfendahl", "scopus_author_id"=>"7005334438"}, {"first_name"=>"Klas", "last_name"=>"Kullander", "scopus_author_id"=>"6701665932"}, {"first_name"=>"Graça", "last_name"=>"Raposo", "scopus_author_id"=>"7003343185"}, {"first_name"=>"Susanne", "last_name"=>"Kerje", "scopus_author_id"=>"6603254094"}, {"first_name"=>"Finn", "last_name"=>"Hallböök", "scopus_author_id"=>"7004743600"}, {"first_name"=>"Michael S.", "last_name"=>"Marks", "scopus_author_id"=>"7201370713"}, {"first_name"=>"Leif", "last_name"=>"Andersson", "scopus_author_id"=>"7403057299"}], "year"=>2011, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"362681113", "issn"=>"15537390", "isbn"=>"1553-7404 (Electronic)\r1553-7390 (Linking)", "doi"=>"10.1371/journal.pgen.1002285", "scopus"=>"2-s2.0-80053436599", "pmid"=>"21949658", "sgr"=>"80053436599"}, "id"=>"43363418-972b-3664-89be-2198c01a4300", "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.", "link"=>"http://www.mendeley.com/research/inactivation-pmel-alters-melanosome-shape-only-subtle-effect-visible-pigmentation", "reader_count"=>52, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>17, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>1, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>17, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>1, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>9, "Materials Science"=>1, "Agricultural and Biological Sciences"=>30, "Medicine and Dentistry"=>6, "Neuroscience"=>2, "Veterinary Science and Veterinary Medicine"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Neuroscience"=>{"Neuroscience"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>30}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>9}, "Unspecified"=>{"Unspecified"=>2}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"United States"=>2, "France"=>1}, "group_count"=>3}

CrossRef

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/735133"], "description"=>"<p>Sections of skin (A) or retina (B, C) from <i>Pmel<sup>+/+</sup></i> (a, b) and <i>Pmel</i><sup>−/−</sup> (c, d) mice were immunolabeled with αPep13h (anti-PMEL) (A, B) or secondary antibody alone (C) and counterstained with DAPI to label nuclei, and analyzed by immunofluorescence microscopy (a, c) or bright field microscopy to assess pigmentation (b, d). (A) PMEL-immunoreactive cells were found in the hair follicles of the skin in wild-type mice (<i>a–b</i>), but not in the <i>Pmel</i><sup>−/−</sup> mice (<i>c–d</i>). Insets, two-fold enlargement of the boxed region. (B) αPep13h immunoreactive cells (green) were found in the choroid (arrowheads) and in the RPE from the <i>Pmel<sup>+/+</sup></i> mouse (<i>a</i>), but only in the RPE/ Bruch's membrane from the <i>Pmel</i><sup>−/−</sup> mouse (<i>c</i>). GCL, ganglion cell layer. (C) Immunostaining obtained using only the secondary anti-rabbit antibody shows a signal from Bruch's membrane. Size bar, 20 µm.</p>", "links"=>[], "tags"=>["retina"], "article_id"=>405472, "categories"=>["Genetics"], "users"=>["Anders R. Hellström", "Brenda Watt", "Shahrzad Shirazi Fard", "Danièle Tenza", "Paula Mannström", "Kristina Narfström", "Björn Ekesten", "Shosuke Ito", "Kazumasa Wakamatsu", "Jimmy Larsson", "Mats Ulfendahl", "Klas Kullander", "Graça Raposo", "Susanne Kerje", "Finn Hallböök", "Michael S. Marks", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002285.g004", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunohistochemistry_of_skin_and_retina_from_Pmel_and_Pmel_8722_8722_mice_/405472", "title"=>"Immunohistochemistry of skin and retina from <i>Pmel<sup>+/+</sup></i>and <i>Pmel<sup>−/−</sup></i>mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-15 01:31:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/734791"], "description"=>"<p>(A) Bright-field microscopy; scale bar, 20µm; inset, 5X magnification. Note that the distribution of melanosomes is similar in both sets of melanocytes. (B) Electron microscopy. Cross-sections of melanosomes in the <i>Pmel<sup>+/+</sup></i> melanocytes are both spherical and rod shaped, whilst they are only spherical in the <i>Pmel</i><sup>−/−</sup> melanocytes. I, II, III, and IV represent stage I, II, III, and IV melanosomes. M, mitochondria; End, endosomes. Note the presence of fibrillar stage II and III melanosomes in the wild-type melanocytes (panel Bb, marked with arrowheads in inset) in contrast to the granular deposits of melanin in <i>Pmel</i><sup>−/−</sup> melanosomes (panel Bd, marked with arrows in inset). Bars: 500 nm and 200 nm, in left and right panels respectively (C) Plot of the diameters of melanosomes along the long (length) and short (width) axes measured from electron microscopy images; n>200 for both genotypes. There was a weak correlation between the length and width of melanosomes in <i>Pmel<sup>+/+</sup></i> cells (r = 0.52), consistent with their ellipsoidal shape, whereas in <i>Pmel</i><sup>−/−</sup> cells, there was a strong correlation (r = 0.93), indicating a spherical shape. The difference in the length/width ratio between wild-type and <i>Pmel</i><sup>−/−</sup> is overwhelmingly significant (Analysis of variance; F = 161, d.f.1 = 1, d.f.2 = 451; P<10<sup>−6</sup>).</p>", "links"=>[], "tags"=>["melanosomes", "observed", "cultures", "skin-derived", "melanocytes", "wild-type"], "article_id"=>405130, "categories"=>["Genetics"], "users"=>["Anders R. Hellström", "Brenda Watt", "Shahrzad Shirazi Fard", "Danièle Tenza", "Paula Mannström", "Kristina Narfström", "Björn Ekesten", "Shosuke Ito", "Kazumasa Wakamatsu", "Jimmy Larsson", "Mats Ulfendahl", "Klas Kullander", "Graça Raposo", "Susanne Kerje", "Finn Hallböök", "Michael S. Marks", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002285.g002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Morphology_of_melanosomes_observed_in_primary_cultures_of_skin_derived_melanocytes_from_wild_type_C57BL_6_Pmel_and_Pmel_8722_8722_mice_/405130", "title"=>"Morphology of melanosomes observed in primary cultures of skin-derived melanocytes from wild-type C57BL/6 (<i>Pmel<sup>+/+</sup></i>) and <i>Pmel<sup>−/−</sup></i>mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-15 01:25:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/735303"], "description"=>"<p>A scale bar is depicted in the lower left hand corner of each micrograph. Melanosomes of both choroidal and RPE cells of the affected animal appear spherical with irregular borders, the latter more obvious in the RPE cells (lower right micrographs, indicated by white arrowheads). Further, no cigar-shaped melanosomes were found in either choroidal or RPE cells in the <i>Pmel</i><sup>−/−</sup> mice.</p>", "links"=>[], "tags"=>["microscopy", "choroidal", "rpe", "cells", "wild-type", "mice"], "article_id"=>405635, "categories"=>["Genetics"], "users"=>["Anders R. Hellström", "Brenda Watt", "Shahrzad Shirazi Fard", "Danièle Tenza", "Paula Mannström", "Kristina Narfström", "Björn Ekesten", "Shosuke Ito", "Kazumasa Wakamatsu", "Jimmy Larsson", "Mats Ulfendahl", "Klas Kullander", "Graça Raposo", "Susanne Kerje", "Finn Hallböök", "Michael S. Marks", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002285.g005", "stats"=>{"downloads"=>2, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Electron_microscopy_of_choroidal_upper_and_lower_left_micrographs_and_RPE_cells_upper_and_lower_right_micrographs_including_melanosomes_from_wild_type_C57BL_6_mice_upper_two_micrographs_and_Pmel_8722_8722_mice_lower_two_micrographs_respectively_/405635", "title"=>"Electron microscopy of choroidal (upper and lower left micrographs) and RPE cells (upper and lower right micrographs), including melanosomes, from wild-type C57BL/6 mice (upper two micrographs) and <i>Pmel<sup>−/−</sup></i> mice (lower two micrographs), respectively.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-15 01:33:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/735631"], "description"=>"<p>The animals depicted in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002285#pgen-1002285-g006\" target=\"_blank\">Figure 6</a> were analyzed.</p>a<p>4-Amino-3-hydroxyphenylalanine (4-AHP), a degradation product of pheomelanin. Pheomelanin content was estimated by multiplying 4-AHP by a factor of 9 <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002285#pgen.1002285-Wakamatsu2\" target=\"_blank\">[36]</a>. Based on a single determination per animal.</p>b<p>Pyrrole-2,3,5-tricarboxylic acid (PTCA), a degradation product of eumelanin <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002285#pgen.1002285-Ito2\" target=\"_blank\">[33]</a>. Eumelanin content was estimated by multiplying PTCA content by a factor of 25. Based on duplicate assays from a single animal/genotype.</p>", "links"=>[], "tags"=>["pheomelanin", "mice"], "article_id"=>405969, "categories"=>["Genetics"], "users"=>["Anders R. Hellström", "Brenda Watt", "Shahrzad Shirazi Fard", "Danièle Tenza", "Paula Mannström", "Kristina Narfström", "Björn Ekesten", "Shosuke Ito", "Kazumasa Wakamatsu", "Jimmy Larsson", "Mats Ulfendahl", "Klas Kullander", "Graça Raposo", "Susanne Kerje", "Finn Hallböök", "Michael S. Marks", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002285.t002", "stats"=>{"downloads"=>3, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Eumelanin_and_pheomelanin_content_in_wild_type_and_PMEL_8722_8722_mice_on_mice_on_different_genetic_backgrounds_/405969", "title"=>"Eumelanin and pheomelanin content in <i>wild-type</i> and <i>PMEL<sup>−/−</sup></i> mice on mice on different genetic backgrounds.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-09-15 01:39:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/734974"], "description"=>"<p>(A) Cells immunolabeled with antibodies against the mature PMEL protein (HMB45, red; <i>a</i>, <i>d</i>, insets) and TYRP1 (green; <i>b</i>, <i>e</i>, insets); the melanosomes were visualized by bright field (<i>c</i>, <i>f</i>) and pseudo-colored blue in the insets. Note the presence of TYRP1 surrounding melanosomes in both sets of melanocytes. (B) Cells immunolabeled with antibodies against the late endosome/ lysosome marker LAMP2 (green; <i>b</i>, <i>e</i>, insets) and TYRP1 (red; <i>a</i>, <i>d</i>, insets); the melanosomes were visualized by bright field (<i>c</i>, <i>f</i>) and pseudo-colored blue in the insets. Note the segregation of LAMP2 labeling from pigment granules labeled by TYRP1. Size bar, 20 µm.</p>", "links"=>[], "tags"=>["microscopy", "melanocytes", "wild-type", "knockout"], "article_id"=>405308, "categories"=>["Genetics"], "users"=>["Anders R. Hellström", "Brenda Watt", "Shahrzad Shirazi Fard", "Danièle Tenza", "Paula Mannström", "Kristina Narfström", "Björn Ekesten", "Shosuke Ito", "Kazumasa Wakamatsu", "Jimmy Larsson", "Mats Ulfendahl", "Klas Kullander", "Graça Raposo", "Susanne Kerje", "Finn Hallböök", "Michael S. Marks", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002285.g003", "stats"=>{"downloads"=>1, "page_views"=>52, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunofluorescence_and_bright_field_microscopy_of_primary_melanocytes_from_C57BL_6_wild_type_Pmel_and_knockout_Pmel_8722_8722_mice_/405308", "title"=>"Immunofluorescence and bright field microscopy of primary melanocytes from C57BL/6 wild-type (<i>Pmel<sup>+/+</sup></i>) and knockout (<i>Pmel</i><sup>−/−</sup>) mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-15 01:28:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/735733"], "description"=>"a<p>Absorbance at 500 nm, a measure of total melanin after Soluene-350 solubilization <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002285#pgen.1002285-Ozeki1\" target=\"_blank\">[34]</a>. Total melanin content was estimated as A500/mg multiplied by a factor of 101.</p>b<p>Pyrrole-2,3,5-tricarboxylic acid (PTCA), a degradation product of eumelanin <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002285#pgen.1002285-Ito2\" target=\"_blank\">[33]</a>. Eumelanin content was estimated by multiplying PTCA content by a factor of 25.</p>c<p>4-Amino-3-hydroxyphenylalanine (4-AHP), a degradation product of pheomelanin. Pheomelanin content was estimated by multiplying 4-AHP by a factor of 9 <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002285#pgen.1002285-Wakamatsu2\" target=\"_blank\">[36]</a>.</p>", "links"=>[], "tags"=>["pheomelanin", "mice"], "article_id"=>406073, "categories"=>["Genetics"], "users"=>["Anders R. Hellström", "Brenda Watt", "Shahrzad Shirazi Fard", "Danièle Tenza", "Paula Mannström", "Kristina Narfström", "Björn Ekesten", "Shosuke Ito", "Kazumasa Wakamatsu", "Jimmy Larsson", "Mats Ulfendahl", "Klas Kullander", "Graça Raposo", "Susanne Kerje", "Finn Hallböök", "Michael S. Marks", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002285.t001", "stats"=>{"downloads"=>11, "page_views"=>38, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Content_of_total_melanin_eumelanin_and_pheomelanin_in_wild_type_and_PMEL_8722_8722_mice_on_a_C57BL_6_background_Asip_a_a_/406073", "title"=>"Content of total melanin, eumelanin, and pheomelanin in <i>wild-type</i> and <i>PMEL<sup>−/−</sup></i> mice on a C57BL/6 background (<i>Asip<sup>a/a</sup></i>).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-09-15 01:41:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/371000", "https://ndownloader.figshare.com/files/371051", "https://ndownloader.figshare.com/files/371135", "https://ndownloader.figshare.com/files/371192"], "description"=>"<div><p>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 <em>Pmel</em> gene has been inactivated (<em>Pmel</em><sup>−/−</sup>). These mice are fully viable, fertile, and display no obvious developmental defects. Melanosomes within <em>Pmel</em><sup>−/−</sup> 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 <em>Pmel</em> has only a mild effect on the coat color phenotype in four different genetic backgrounds, with the clearest effect in mice also carrying the <em>brown/Tyrp1</em> mutation. This phenotype, which is similar to that observed with the spontaneous <em>silver</em> 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 <em>Pmel</em> led to a substantial reduction in eumelanin content in hair, which demonstrates that PMEL has a critical role for maintaining efficient epidermal pigmentation.</p> </div>", "links"=>[], "tags"=>["inactivation", "alters", "melanosome", "pigmentation"], "article_id"=>133290, "categories"=>["Genetics"], "users"=>["Anders R. Hellström", "Brenda Watt", "Shahrzad Shirazi Fard", "Danièle Tenza", "Paula Mannström", "Kristina Narfström", "Björn Ekesten", "Shosuke Ito", "Kazumasa Wakamatsu", "Jimmy Larsson", "Mats Ulfendahl", "Klas Kullander", "Graça Raposo", "Susanne Kerje", "Finn Hallböök", "Michael S. Marks", "Leif Andersson"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002285.s001", "https://dx.doi.org/10.1371/journal.pgen.1002285.s002", "https://dx.doi.org/10.1371/journal.pgen.1002285.s003", "https://dx.doi.org/10.1371/journal.pgen.1002285.s004"], "stats"=>{"downloads"=>6, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Inactivation_of_Pmel_Alters_Melanosome_Shape_But_Has_Only_a_Subtle_Effect_on_Visible_Pigmentation/133290", "title"=>"Inactivation of <em>Pmel</em> Alters Melanosome Shape But Has Only a Subtle Effect on Visible Pigmentation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-09-15 00:54:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/735690"], "description"=>"<p>Data generated by the 1000 genome project.</p>", "links"=>[], "tags"=>["frequencies", "non-reference", "allele", "locus", "chromosome", "12", "african", "european", "asian"], "article_id"=>406021, "categories"=>["Genetics"], "users"=>["Anders R. Hellström", "Brenda Watt", "Shahrzad Shirazi Fard", "Danièle Tenza", "Paula Mannström", "Kristina Narfström", "Björn Ekesten", "Shosuke Ito", "Kazumasa Wakamatsu", "Jimmy Larsson", "Mats Ulfendahl", "Klas Kullander", "Graça Raposo", "Susanne Kerje", "Finn Hallböök", "Michael S. Marks", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002285.t003", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Observed_frequencies_of_the_non_reference_allele_at_the_human_PMEL_locus_on_chromosome_12_in_African_YRI_European_CEU_and_Asian_CHJPT_populations_/406021", "title"=>"Observed frequencies of the non-reference allele at the human <i>PMEL</i> locus on chromosome 12 in African (YRI), European (CEU), and Asian (CHJPT) populations.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-09-15 01:40:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/735498"], "description"=>"<p>Coat color was assessed in different genetic backgrounds by pairwise comparisons from an F<sub>2</sub> intercross generation. Within each pair, the <i>Pmel</i><sup>−/−</sup> and <i>Pmel<sup>+/+</sup></i> mice are to the left and right, respectively. (<i>a</i>) The non-agouti black (<i>Asip<sup>a/a</sup></i>) <i>Pmel</i><sup>−/−</sup> mice displayed a subtle dilution of coat color and tail skin. (<i>b</i>) PMEL inactivation in brown mice (<i>Asip<sup>a/a</sup> Tyrp1<sup>b/b</sup></i>) caused the most dramatic reduction in coat color and tail skin pigmentation. (<i>c</i>) The black hairs of the <i>Pmel</i><sup>−/−</sup> mice on brown agouti (<i>Asip<sup>A/−</sup> Tyrp1<sup>b/b</sup></i>) background was diluted giving the coat a more yellow/light brown appearance compared to the wild-type. (<i>d</i>) The weakest phenotypic effect associated with the <i>Pmel</i><sup>−/−</sup> genotype was seen in agouti mice (<i>Asip<sup>A/−</sup></i>) but the coat and skin color were slightly lighter relative to the wild-type. (<i>e, f</i>) The skin of the feet of non-agouti black (<i>Asip<sup>a/a</sup></i>) <i>Pmel</i><sup>−/−</sup> mice were less pigmented compared to the wild-type.</p>", "links"=>[], "tags"=>["pigmentation", "genotype"], "article_id"=>405843, "categories"=>["Genetics"], "users"=>["Anders R. Hellström", "Brenda Watt", "Shahrzad Shirazi Fard", "Danièle Tenza", "Paula Mannström", "Kristina Narfström", "Björn Ekesten", "Shosuke Ito", "Kazumasa Wakamatsu", "Jimmy Larsson", "Mats Ulfendahl", "Klas Kullander", "Graça Raposo", "Susanne Kerje", "Finn Hallböök", "Michael S. Marks", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002285.g006", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phenotypic_effects_on_pigmentation_of_the_Pmel_8722_8722_genotype_on_four_different_genetic_backgrounds_/405843", "title"=>"Phenotypic effects on pigmentation of the <i>Pmel<sup>−/−</sup></i> genotype on four different genetic backgrounds.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-15 01:37:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/734651"], "description"=>"<p>(A) Schematic representation of the <i>Pmel<sup>+</sup></i>, <i>Pmel<sup>loxP</sup></i>, and <i>Pmel<sup>−</sup></i> alleles. The exons (gray boxes), primers used for genotyping (black arrowheads), KpnI restriction cleavage sites and the target site of Southern blot probe (SP, black box) are all indicated. In the <i>Pmel<sup>loxP</sup></i> allele, exon 2 and exon 3 are loxP-flanked (red circles) and a neomycin (green box) gene is flanked by two FRT-sites (blue boxes). In the <i>Pmel<sup>−</sup></i> allele, exon 2 and exon 3 are deleted after Cre-recombinase induced homologous recombination between the loxP sites. (B) Southern blot showing targeted and control ES-cells. The wild-type and the <i>Pmel<sup>loxP</sup></i> alleles generate a 9.7 kb band and a 7.7 kb band, respectively. (C) <i>Pmel</i> mRNA expression. A 1.9-fold change was detected in skin tissue when homozygous <i>Pmel<sup>+/+</sup></i> mice were compared to <i>Pmel</i><sup>+/−</sup> heterozygotes. A 279-fold change was detected when homozygous <i>Pmel</i><sup>−/−</sup> mice were compared to homozygous wild-type mice. (D) Western blot analysis. Whole cell lysates from primary cultures of skin-derived melanocytes from <i>wild-type</i> (mel Pmel<sup>+/+</sup>) or <i>Pmel</i><sup>−/−</sup> (mel Pmel<sup>−/−</sup>) C57BL/6 mice were used, and lysates from transfected HeLa cells expressing human PMEL (HeLa hPMEL) or untransfected human fibroblasts (Fibrobl) were used as positive and negative controls. The lysates were fractionated by SDS-PAGE and analyzed by immunoblotting with a panel of antibodies directed against PMEL (αmPmel-N, HMB45, and αPep13h) or the control proteins, tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and γ-tubulin. αmPmel-N recognizes an N-terminal peptide from mouse PMEL; HMB45 recognizes an epitope derived from the central region of PMEL that is enriched on fibrils; and αPep13h detects the PMEL C-terminus. Migration of molecular weight markers (in kDa) is shown to the left, and relevant bands are indicated to the right.</p>", "links"=>[], "tags"=>["validation"], "article_id"=>404991, "categories"=>["Genetics"], "users"=>["Anders R. Hellström", "Brenda Watt", "Shahrzad Shirazi Fard", "Danièle Tenza", "Paula Mannström", "Kristina Narfström", "Björn Ekesten", "Shosuke Ito", "Kazumasa Wakamatsu", "Jimmy Larsson", "Mats Ulfendahl", "Klas Kullander", "Graça Raposo", "Susanne Kerje", "Finn Hallböök", "Michael S. Marks", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002285.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Strategy_for_the_generation_and_validation_of_Pmel_8722_8722_mice_/404991", "title"=>"Strategy for the generation and validation of <i>Pmel<sup>−/−</sup></i> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-15 01:23:11"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"15", "full-text"=>"15", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
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  • {"unique-ip"=>"16", "full-text"=>"24", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
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Relative Metric

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