Identification of Genes Important for Cutaneous Function Revealed by a Large Scale Reverse Genetic Screen in the Mouse
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{"title"=>"Identification of Genes Important for Cutaneous Function Revealed by a Large Scale Reverse Genetic Screen in the Mouse", "type"=>"journal", "authors"=>[{"first_name"=>"Tia", "last_name"=>"DiTommaso", "scopus_author_id"=>"35755311500"}, {"first_name"=>"Lynelle K.", "last_name"=>"Jones", "scopus_author_id"=>"55464916900"}, {"first_name"=>"Denny L.", "last_name"=>"Cottle", "scopus_author_id"=>"13403866400"}, {"first_name"=>"Anna Karin", "last_name"=>"Gerdin", "scopus_author_id"=>"6507855461"}, {"first_name"=>"Valerie E.", "last_name"=>"Vancollie", "scopus_author_id"=>"57192060687"}, {"first_name"=>"Fiona M.", "last_name"=>"Watt", "scopus_author_id"=>"7102810626"}, {"first_name"=>"Ramiro", "last_name"=>"Ramirez-Solis", "scopus_author_id"=>"6602187588"}, {"first_name"=>"Allan", "last_name"=>"Bradley", "scopus_author_id"=>"57098086000"}, {"first_name"=>"Karen P.", "last_name"=>"Steel", "scopus_author_id"=>"7102712349"}, {"first_name"=>"John P.", "last_name"=>"Sundberg", "scopus_author_id"=>"7102582077"}, {"first_name"=>"Jacqueline K.", "last_name"=>"White", "scopus_author_id"=>"57125207100"}, {"first_name"=>"Ian M.", "last_name"=>"Smyth", "scopus_author_id"=>"6701821279"}], "year"=>2014, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537404", "scopus"=>"2-s2.0-84908315165", "sgr"=>"84908315165", "pui"=>"600311150", "isbn"=>"2006037188", "pmid"=>"25340873", "doi"=>"10.1371/journal.pgen.1004705"}, "id"=>"2b944124-2b79-3022-b015-3d0e44bc63fb", "abstract"=>"The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP). A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1), while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1). The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.", "link"=>"http://www.mendeley.com/research/identification-genes-important-cutaneous-function-revealed-large-scale-reverse-genetic-screen-mouse", "reader_count"=>27, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>6, "Agricultural and Biological Sciences"=>11, "Medicine and Dentistry"=>3, "Veterinary Science and Veterinary Medicine"=>1, "Physics and Astronomy"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>3}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Germany"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1728352"], "description"=>"<p>Genes identified in the primary phenotypic screen with cutaneous defects.</p>", "links"=>[], "tags"=>["cutaneous functions", "screening protocols", "large scale", "screening approach", "histological change", "regenerative organ", "hair follicle cycling", "marker expression", "Mouse Genetics Project", "skin disease", "Genetic Screen", "Cutaneous lesions", "Skin development", "health issue", "phenotyping pipelines marks", "cutaneous expression", "future projects", "Cutaneous Function Revealed", "Wellcome Trust Sanger Institute", "mouse lines", "skin defects"], "article_id"=>1213261, "categories"=>["Uncategorised"], "users"=>["Tia DiTommaso", "Lynelle K. Jones", "Denny L. Cottle", "Anna-Karin Gerdin", "Valerie E. Vancollie", "Fiona M. Watt", "Ramiro Ramirez-Solis", "Allan Bradley", "Karen P. Steel", "John P. Sundberg", "Jacqueline K. White", "Ian M. Smyth"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004705.t001", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Genes_identified_in_the_primary_phenotypic_screen_with_cutaneous_defects_/1213261", "title"=>"Genes identified in the primary phenotypic screen with cutaneous defects.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-10-23 02:42:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1728351"], "description"=>"<p>Each of the 3 different tests identified genes that were represented in other screens (shared) as well as genes that were unique to the test (A). Histopathology screen identified the highest number of unique genes flagged with 79% (n = 11/14) of genes not represented in any other skin screen. Different screens highlighted 25 unique MP terms, with only 1 MP term represented in multiple tests (B). Twenty three unique genes were identified across the 3 different skin tests with 4 represented in multiple tests (C).</p>", "links"=>[], "tags"=>["cutaneous functions", "screening protocols", "large scale", "screening approach", "histological change", "regenerative organ", "hair follicle cycling", "marker expression", "Mouse Genetics Project", "skin disease", "Genetic Screen", "Cutaneous lesions", "Skin development", "health issue", "phenotyping pipelines marks", "cutaneous expression", "future projects", "Cutaneous Function Revealed", "Wellcome Trust Sanger Institute", "mouse lines", "skin defects"], "article_id"=>1213260, "categories"=>["Uncategorised"], "users"=>["Tia DiTommaso", "Lynelle K. Jones", "Denny L. Cottle", "Anna-Karin Gerdin", "Valerie E. Vancollie", "Fiona M. Watt", "Ramiro Ramirez-Solis", "Allan Bradley", "Karen P. Steel", "John P. Sundberg", "Jacqueline K. White", "Ian M. Smyth"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004705.g005", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Multi_parameter_multi_test_organ_specific_screens_add_to_the_number_of_genes_identified_in_skin_biology_/1213260", "title"=>"Multi parameter, multi test, organ specific screens add to the number of genes identified in skin biology.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-23 02:42:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1728338"], "description"=>"<p><i>Mysm1<sup>tm1a/tm1a</sup></i> mice exhibited a range of pigmentation defects, including belly spots, and foot pad hyper-pigmentation (A, B, C). <i>LacZ</i> reporter expression of <i>Mysm1</i> is detected in the paw pad (D), dorsal skin and tail (E,F) whole mounts. Tail whole mount labelled with Keratin 14 (KRT14, red) and Keratin 15 (KRT15, green) indicate defects in hair follicle organization and associated structures in <i>Mysm1</i> knockouts (H) compared to heterozygotes (G). I) Analysis of footpad pigmentation in male <i>Vangl1<sup>tm1a/tm1a</sup></i> mice. J,K) <i>LacZ</i> reporter expression of <i>Vangl1</i> in the ear skin (pinna) and tail whole mounts.</p>", "links"=>[], "tags"=>["cutaneous functions", "screening protocols", "large scale", "screening approach", "histological change", "regenerative organ", "hair follicle cycling", "marker expression", "Mouse Genetics Project", "skin disease", "Genetic Screen", "Cutaneous lesions", "Skin development", "health issue", "phenotyping pipelines marks", "cutaneous expression", "future projects", "Cutaneous Function Revealed", "Wellcome Trust Sanger Institute", "mouse lines", "skin defects"], "article_id"=>1213256, "categories"=>["Uncategorised"], "users"=>["Tia DiTommaso", "Lynelle K. Jones", "Denny L. Cottle", "Anna-Karin Gerdin", "Valerie E. Vancollie", "Fiona M. Watt", "Ramiro Ramirez-Solis", "Allan Bradley", "Karen P. Steel", "John P. Sundberg", "Jacqueline K. White", "Ian M. Smyth"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004705.g003", "stats"=>{"downloads"=>0, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Examples_of_pigmentation_phenotypes_and_expression_patterns_in_genes_with_novel_roles_in_skin_biology_/1213256", "title"=>"Examples of pigmentation phenotypes and expression patterns in genes with novel roles in skin biology.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-23 02:42:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1728353", "https://ndownloader.figshare.com/files/1728354", "https://ndownloader.figshare.com/files/1728355", "https://ndownloader.figshare.com/files/1728356", "https://ndownloader.figshare.com/files/1728357"], "description"=>"<div><p>The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP). A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (<i>Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2</i>, and <i>Prkab1</i>), while others were ascribed new cutaneous functions on the basis of the screening approach (<i>Krt76, Lrig1, Myo5a, Nsun2</i>, and <i>Nf1</i>). The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.</p></div>", "links"=>[], "tags"=>["cutaneous functions", "screening protocols", "large scale", "screening approach", "histological change", "regenerative organ", "hair follicle cycling", "marker expression", "Mouse Genetics Project", "skin disease", "Genetic Screen", "Cutaneous lesions", "Skin development", "health issue", "phenotyping pipelines marks", "cutaneous expression", "future projects", "Cutaneous Function Revealed", "Wellcome Trust Sanger Institute", "mouse lines", "skin defects"], "article_id"=>1213262, "categories"=>["Uncategorised"], "users"=>["Tia DiTommaso", "Lynelle K. Jones", "Denny L. Cottle", "Anna-Karin Gerdin", "Valerie E. Vancollie", "Fiona M. Watt", "Ramiro Ramirez-Solis", "Allan Bradley", "Karen P. Steel", "John P. Sundberg", "Jacqueline K. White", "Ian M. Smyth"], "doi"=>[nil, nil, nil, nil, nil], "stats"=>{"downloads"=>8, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Identification_of_Genes_Important_for_Cutaneous_Function_Revealed_by_a_Large_Scale_Reverse_Genetic_Screen_in_the_Mouse/1213262", "title"=>"Identification of Genes Important for Cutaneous Function Revealed by a Large Scale Reverse Genetic Screen in the Mouse", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-10-23 02:42:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1728350"], "description"=>"<p><i>Nsun2</i> expression was reported by <i>lacZ</i> staining in <i>Nsun2<sup>tm1a</sup>/+</i> mice in the hair follicles of murine dorsal skin (A,B), the outer ear pinna (C), and tail (D). <i>Nsun2</i> mice demonstrated evidence of premature separation of the club hair from the surrounding follicle, leaving an empty area or breakage (E see arrowhead, Fi-v) in contrast to a normal follicle (G). <i>Lrig1</i> expression was reported by <i>lacZ</i> staining in <i>Lrig1<sup>tm1a/+</sup></i> mice in the developing epidermis and dermis of E14.5 skin (H), the developing hair follicle and upper dermis of E18.5 skin (I), the upper dermis and junctional zone above sebaceous glands in adult skin (J), the hair follicles of adult murine dorsal skin (K), the outer ear pinna (L) and inguinal fat pads (M). <i>Lrig1</i> mice also demonstrate premature separation of the club hair (N). <i>Farp2</i> expression was reported by weak <i>lacZ</i> staining in footpads and dermis of <i>Farp2<sup>tm1a/+</sup></i> mice (O,P see arrowhead). <i>Farp2</i> mice also demonstrated premature separation of the club hair (Q). Scale bars are 50 µm.</p>", "links"=>[], "tags"=>["cutaneous functions", "screening protocols", "large scale", "screening approach", "histological change", "regenerative organ", "hair follicle cycling", "marker expression", "Mouse Genetics Project", "skin disease", "Genetic Screen", "Cutaneous lesions", "Skin development", "health issue", "phenotyping pipelines marks", "cutaneous expression", "future projects", "Cutaneous Function Revealed", "Wellcome Trust Sanger Institute", "mouse lines", "skin defects"], "article_id"=>1213259, "categories"=>["Uncategorised"], "users"=>["Tia DiTommaso", "Lynelle K. Jones", "Denny L. Cottle", "Anna-Karin Gerdin", "Valerie E. Vancollie", "Fiona M. Watt", "Ramiro Ramirez-Solis", "Allan Bradley", "Karen P. Steel", "John P. Sundberg", "Jacqueline K. White", "Ian M. Smyth"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004705.g004", "stats"=>{"downloads"=>0, "page_views"=>47, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/High_throughput_screening_provides_insights_into_molecular_mechanisms_of_exogen_in_hair_follicle_cycling_/1213259", "title"=>"High throughput screening provides insights into molecular mechanisms of exogen in hair follicle cycling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-23 02:42:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1728335"], "description"=>"<p>(A) The dorsal skin of 44 wild type mice and 514 mutant mice were assessed by an expert dermatologist. 3 wild type mice and 30 targeted alleles (in 30 mutant strains) showed abnormalities in one or more of the phenotypic categories listed (35 abnormalities total). The phenotypes of abnormal hair shaft morphology and skin inflammation were observed in both wild type and mutants and taken to be a background phenotype, therefore were not considered significant in the overall phenotypic analysis. Wild type images for comparison are shown in (B) and (F). Phenotypes unique to mutant animals included abnormal hypodermis dermis morphology (C,D), abnormal pigmentation (E) and abnormally prominent arrector pilli muscle (G). More specifically, <i>Aldh18a1<sup>tm1a</sup>/+</i> mice presented with mild, multifocal mixed inflammatory cell infiltration with mild fibrosis and distortion of adipocytes in the hypodermal fat layer potentially indicating abnormalities in white fat cells (C). <i>Prmt3<sup>tm1a/tm1a</sup></i> mutant mice exhibited granulomatous steatitis (red arrowheads) (D). <i>Arpc1b<sup>tm1a/tm1a</sup></i> mutant mice had mild to moderate multifocal areas of dermal fibrosis with pigment laden macrophages (yellow arrows) suggesting hair follicle rupture (E). <i>Rad18<sup>tm1a/tm1a</sup></i> mutant mice had normal skin but unusually prominent arrector pili muscles (black arrows) (G). Scale bars are 50 µm.</p>", "links"=>[], "tags"=>["cutaneous functions", "screening protocols", "large scale", "screening approach", "histological change", "regenerative organ", "hair follicle cycling", "marker expression", "Mouse Genetics Project", "skin disease", "Genetic Screen", "Cutaneous lesions", "Skin development", "health issue", "phenotyping pipelines marks", "cutaneous expression", "future projects", "Cutaneous Function Revealed", "Wellcome Trust Sanger Institute", "mouse lines", "skin defects"], "article_id"=>1213253, "categories"=>["Uncategorised"], "users"=>["Tia DiTommaso", "Lynelle K. Jones", "Denny L. Cottle", "Anna-Karin Gerdin", "Valerie E. Vancollie", "Fiona M. Watt", "Ramiro Ramirez-Solis", "Allan Bradley", "Karen P. Steel", "John P. Sundberg", "Jacqueline K. White", "Ian M. Smyth"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004705.g002", "stats"=>{"downloads"=>2, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Skin_histopathology_overview_/1213253", "title"=>"Skin histopathology overview.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-23 02:42:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1728331"], "description"=>"<p>A) Flow-chart illulstrating pipeline of skin phenotyping. B–E) Examples of obvious coat phenotypes in <i>Myo5a, Lrig1</i> and <i>Nsun2</i> strains relative to wild-type mice. F) 10 male and 10 female pigmented wild type mice were shaved and skin colour assessed from 35–53 days of age. Results are shown in a grid where cell color represents skin colour. Black indicates anagen, shades of grey (and dark pink) indicate catagen, pale pink indicates telogen for males, pink indicates telogen for females, and crosses indicate days mice were not assessed. Mutant mice and matched wild type controls were next shaved in weekly cohorts and dorsal skin assessed for hair cycle phase using the skin color method above at an age of 41–43 days. Pigmented mice were assessed as normal (grey skin/in catagen), non synchronous (mixed patches of hair cycle phases), and anagen (black skin). Albino mice could not be assessed and were excluded from the analysis. G–K) Shows <i>Nf1<sup>tm1a</sup></i>; <i>Nsun2<sup>tm1a</sup></i>; <i>Myo5a<sup>tm1e</sup></i>; <i>Trpc4ap<sup>tm1a</sup></i>; <i>Nom1<sup>tm1a</sup></i> demonstrated signs of abnormally in constrast to their wild type controls. L) Table summarises wild type findings for baseline reference.</p>", "links"=>[], "tags"=>["cutaneous functions", "screening protocols", "large scale", "screening approach", "histological change", "regenerative organ", "hair follicle cycling", "marker expression", "Mouse Genetics Project", "skin disease", "Genetic Screen", "Cutaneous lesions", "Skin development", "health issue", "phenotyping pipelines marks", "cutaneous expression", "future projects", "Cutaneous Function Revealed", "Wellcome Trust Sanger Institute", "mouse lines", "skin defects"], "article_id"=>1213249, "categories"=>["Uncategorised"], "users"=>["Tia DiTommaso", "Lynelle K. Jones", "Denny L. Cottle", "Anna-Karin Gerdin", "Valerie E. Vancollie", "Fiona M. Watt", "Ramiro Ramirez-Solis", "Allan Bradley", "Karen P. Steel", "John P. Sundberg", "Jacqueline K. White", "Ian M. Smyth"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004705.g001", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Overview_of_pipeline_hair_follicle_cycling_baseline_and_phenotypes_/1213249", "title"=>"Overview of pipeline, hair follicle cycling baseline and phenotypes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-23 02:42:11"}

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Relative Metric

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