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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. Skin and adne...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503261/ https://www.ncbi.nlm.nih.gov/pubmed/28700664 http://dx.doi.org/10.1371/journal.pone.0180682 |
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author | 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 |
author_facet | 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 |
author_sort | Sundberg, John P. |
collection | PubMed |
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)-Far2(tm2b(KOMP)Wtsi)/2J strain, had lesions affecting sebaceous glands with what appeared to be a secondary follicular dystrophy. A second line, B6N(Cg)-Ppp1r9b(tm1.1(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. |
format | Online Article Text |
id | pubmed-5503261 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55032612017-07-25 Systematic screening for skin, hair, and nail abnormalities in a large-scale knockout mouse program 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 PLoS One Research Article 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)-Far2(tm2b(KOMP)Wtsi)/2J strain, had lesions affecting sebaceous glands with what appeared to be a secondary follicular dystrophy. A second line, B6N(Cg)-Ppp1r9b(tm1.1(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. Public Library of Science 2017-07-10 /pmc/articles/PMC5503261/ /pubmed/28700664 http://dx.doi.org/10.1371/journal.pone.0180682 Text en © 2017 Sundberg et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article 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 Systematic screening for skin, hair, and nail abnormalities in a large-scale knockout mouse program |
title | Systematic screening for skin, hair, and nail abnormalities in a large-scale knockout mouse program |
title_full | Systematic screening for skin, hair, and nail abnormalities in a large-scale knockout mouse program |
title_fullStr | Systematic screening for skin, hair, and nail abnormalities in a large-scale knockout mouse program |
title_full_unstemmed | Systematic screening for skin, hair, and nail abnormalities in a large-scale knockout mouse program |
title_short | Systematic screening for skin, hair, and nail abnormalities in a large-scale knockout mouse program |
title_sort | systematic screening for skin, hair, and nail abnormalities in a large-scale knockout mouse program |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503261/ https://www.ncbi.nlm.nih.gov/pubmed/28700664 http://dx.doi.org/10.1371/journal.pone.0180682 |
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