Systematic screening for skin, hair, and nail abnormalities in a large-scale knockout mouse program
The International Knockout Mouse Consortium was formed in 2007 to inactivate ("knockout") all protein-coding genes in the mouse genome in embryonic stem cells. Production and characterization of these mice, now underway, has generated and phenotyped 3,100 strains with knockout alleles. Ski...
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| Veröffentlicht in: | PloS one 2017-07, Vol.12 (7), p.e0180682-e0180682 |
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| creator | Sundberg, John P Dadras, Soheil S Silva, Kathleen A Kennedy, Victoria E Garland, Gaven Murray, Stephen A Sundberg, Beth A Schofield, Paul N Pratt, C Herbert |
| description | The International Knockout Mouse Consortium was formed in 2007 to inactivate ("knockout") all protein-coding genes in the mouse genome in embryonic stem cells. Production and characterization of these mice, now underway, has generated and phenotyped 3,100 strains with knockout alleles. Skin and adnexa diseases are best defined at the gross clinical level and by histopathology. Representative retired breeders had skin collected from the back, abdomen, eyelids, muzzle, ears, tail, and lower limbs including the nails. To date, 169 novel mutant lines were reviewed and of these, only one was found to have a relatively minor sebaceous gland abnormality associated with follicular dystrophy. The B6N(Cg)-Far2tm2b(KOMP)Wtsi/2J strain, had lesions affecting sebaceous glands with what appeared to be a secondary follicular dystrophy. A second line, B6N(Cg)-Ppp1r9btm1.1(KOMP)Vlcg/J, had follicular dystrophy limited to many but not all mystacial vibrissae in heterozygous but not homozygous mutant mice, suggesting that this was a nonspecific background lesion. We discuss potential reasons for the low frequency of skin and adnexal phenotypes in mice from this project in comparison to those seen in human Mendelian diseases, and suggest alternative approaches to identification of human disease-relevant models. |
| doi_str_mv | 10.1371/journal.pone.0180682 |
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Production and characterization of these mice, now underway, has generated and phenotyped 3,100 strains with knockout alleles. Skin and adnexa diseases are best defined at the gross clinical level and by histopathology. Representative retired breeders had skin collected from the back, abdomen, eyelids, muzzle, ears, tail, and lower limbs including the nails. To date, 169 novel mutant lines were reviewed and of these, only one was found to have a relatively minor sebaceous gland abnormality associated with follicular dystrophy. The B6N(Cg)-Far2tm2b(KOMP)Wtsi/2J strain, had lesions affecting sebaceous glands with what appeared to be a secondary follicular dystrophy. A second line, B6N(Cg)-Ppp1r9btm1.1(KOMP)Vlcg/J, had follicular dystrophy limited to many but not all mystacial vibrissae in heterozygous but not homozygous mutant mice, suggesting that this was a nonspecific background lesion. We discuss potential reasons for the low frequency of skin and adnexal phenotypes in mice from this project in comparison to those seen in human Mendelian diseases, and suggest alternative approaches to identification of human disease-relevant models.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0180682</identifier><identifier>PMID: 28700664</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abdomen ; Abnormalities ; Animal models ; Animals ; Biology and Life Sciences ; Consortia ; Dystrophy ; Embryo cells ; Genomes ; Genomics ; Glands ; Hair ; Hair - abnormalities ; Histopathology ; Laboratories ; Lesions ; Limbs ; Low frequencies ; Medical screening ; Medicine and Health Sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation ; Nails (Anatomy) ; Nails, Malformed - genetics ; Research and Analysis Methods ; Reviews ; Rodents ; Sebaceous gland ; Sebaceous glands ; Sebaceous Glands - pathology ; Skin - pathology ; Skin Abnormalities - genetics ; Skin diseases ; Social Sciences ; Stem cell transplantation ; Stem cells ; Vibrissae ; Vibrissae - pathology</subject><ispartof>PloS one, 2017-07, Vol.12 (7), p.e0180682-e0180682</ispartof><rights>2017 Sundberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Production and characterization of these mice, now underway, has generated and phenotyped 3,100 strains with knockout alleles. Skin and adnexa diseases are best defined at the gross clinical level and by histopathology. Representative retired breeders had skin collected from the back, abdomen, eyelids, muzzle, ears, tail, and lower limbs including the nails. To date, 169 novel mutant lines were reviewed and of these, only one was found to have a relatively minor sebaceous gland abnormality associated with follicular dystrophy. The B6N(Cg)-Far2tm2b(KOMP)Wtsi/2J strain, had lesions affecting sebaceous glands with what appeared to be a secondary follicular dystrophy. A second line, B6N(Cg)-Ppp1r9btm1.1(KOMP)Vlcg/J, had follicular dystrophy limited to many but not all mystacial vibrissae in heterozygous but not homozygous mutant mice, suggesting that this was a nonspecific background lesion. We discuss potential reasons for the low frequency of skin and adnexal phenotypes in mice from this project in comparison to those seen in human Mendelian diseases, and suggest alternative approaches to identification of human disease-relevant models.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28700664</pmid><doi>10.1371/journal.pone.0180682</doi><orcidid>https://orcid.org/0000-0002-1523-5430</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Abdomen Abnormalities Animal models Animals Biology and Life Sciences Consortia Dystrophy Embryo cells Genomes Genomics Glands Hair Hair - abnormalities Histopathology Laboratories Lesions Limbs Low frequencies Medical screening Medicine and Health Sciences Mice Mice, Inbred C57BL Mice, Knockout Mutation Nails (Anatomy) Nails, Malformed - genetics Research and Analysis Methods Reviews Rodents Sebaceous gland Sebaceous glands Sebaceous Glands - pathology Skin - pathology Skin Abnormalities - genetics Skin diseases Social Sciences Stem cell transplantation Stem cells Vibrissae Vibrissae - pathology |
| title | Systematic screening for skin, hair, and nail abnormalities in a large-scale knockout mouse program |
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