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Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen

The Mouse Genetics Project (MGP) at the Wellcome Trust Sanger Institute aims to generate and phenotype over 800 genetically modified mouse lines over the next 5 years to gain a better understanding of mammalian gene function and provide an invaluable resource to the scientific community for follow-u...

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Autores principales: Adissu, Hibret A., Estabel, Jeanne, Sunter, David, Tuck, Elizabeth, Hooks, Yvette, Carragher, Damian M., Clarke, Kay, Karp, Natasha A., Project, Sanger Mouse Genetics, Newbigging, Susan, Jones, Nora, Morikawa, Lily, White, Jacqueline K., McKerlie, Colin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Limited 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007403/
https://www.ncbi.nlm.nih.gov/pubmed/24652767
http://dx.doi.org/10.1242/dmm.015263
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author Adissu, Hibret A.
Estabel, Jeanne
Sunter, David
Tuck, Elizabeth
Hooks, Yvette
Carragher, Damian M.
Clarke, Kay
Karp, Natasha A.
Project, Sanger Mouse Genetics
Newbigging, Susan
Jones, Nora
Morikawa, Lily
White, Jacqueline K.
McKerlie, Colin
author_facet Adissu, Hibret A.
Estabel, Jeanne
Sunter, David
Tuck, Elizabeth
Hooks, Yvette
Carragher, Damian M.
Clarke, Kay
Karp, Natasha A.
Project, Sanger Mouse Genetics
Newbigging, Susan
Jones, Nora
Morikawa, Lily
White, Jacqueline K.
McKerlie, Colin
author_sort Adissu, Hibret A.
collection PubMed
description The Mouse Genetics Project (MGP) at the Wellcome Trust Sanger Institute aims to generate and phenotype over 800 genetically modified mouse lines over the next 5 years to gain a better understanding of mammalian gene function and provide an invaluable resource to the scientific community for follow-up studies. Phenotyping includes the generation of a standardized biobank of paraffin-embedded tissues for each mouse line, but histopathology is not routinely performed. In collaboration with the Pathology Core of the Centre for Modeling Human Disease (CMHD) we report the utility of histopathology in a high-throughput primary phenotyping screen. Histopathology was assessed in an unbiased selection of 50 mouse lines with (n=30) or without (n=20) clinical phenotypes detected by the standard MGP primary phenotyping screen. Our findings revealed that histopathology added correlating morphological data in 19 of 30 lines (63.3%) in which the primary screen detected a phenotype. In addition, seven of the 50 lines (14%) presented significant histopathology findings that were not associated with or predicted by the standard primary screen. Three of these seven lines had no clinical phenotype detected by the standard primary screen. Incidental and strain-associated background lesions were present in all mutant lines with good concordance to wild-type controls. These findings demonstrate the complementary and unique contribution of histopathology to high-throughput primary phenotyping of mutant mice.
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spelling pubmed-40074032014-05-14 Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen Adissu, Hibret A. Estabel, Jeanne Sunter, David Tuck, Elizabeth Hooks, Yvette Carragher, Damian M. Clarke, Kay Karp, Natasha A. Project, Sanger Mouse Genetics Newbigging, Susan Jones, Nora Morikawa, Lily White, Jacqueline K. McKerlie, Colin Dis Model Mech Research Article The Mouse Genetics Project (MGP) at the Wellcome Trust Sanger Institute aims to generate and phenotype over 800 genetically modified mouse lines over the next 5 years to gain a better understanding of mammalian gene function and provide an invaluable resource to the scientific community for follow-up studies. Phenotyping includes the generation of a standardized biobank of paraffin-embedded tissues for each mouse line, but histopathology is not routinely performed. In collaboration with the Pathology Core of the Centre for Modeling Human Disease (CMHD) we report the utility of histopathology in a high-throughput primary phenotyping screen. Histopathology was assessed in an unbiased selection of 50 mouse lines with (n=30) or without (n=20) clinical phenotypes detected by the standard MGP primary phenotyping screen. Our findings revealed that histopathology added correlating morphological data in 19 of 30 lines (63.3%) in which the primary screen detected a phenotype. In addition, seven of the 50 lines (14%) presented significant histopathology findings that were not associated with or predicted by the standard primary screen. Three of these seven lines had no clinical phenotype detected by the standard primary screen. Incidental and strain-associated background lesions were present in all mutant lines with good concordance to wild-type controls. These findings demonstrate the complementary and unique contribution of histopathology to high-throughput primary phenotyping of mutant mice. The Company of Biologists Limited 2014-05 2014-03-20 /pmc/articles/PMC4007403/ /pubmed/24652767 http://dx.doi.org/10.1242/dmm.015263 Text en © 2014. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Adissu, Hibret A.
Estabel, Jeanne
Sunter, David
Tuck, Elizabeth
Hooks, Yvette
Carragher, Damian M.
Clarke, Kay
Karp, Natasha A.
Project, Sanger Mouse Genetics
Newbigging, Susan
Jones, Nora
Morikawa, Lily
White, Jacqueline K.
McKerlie, Colin
Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen
title Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen
title_full Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen
title_fullStr Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen
title_full_unstemmed Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen
title_short Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen
title_sort histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007403/
https://www.ncbi.nlm.nih.gov/pubmed/24652767
http://dx.doi.org/10.1242/dmm.015263
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