Genotypic analysis of the female BPH/5 mouse, a model of superimposed preeclampsia.

Animal models that recapitulate human diseases and disorders are widely used to investigate etiology, diagnosis, and treatment of those conditions in people. Disorders during pregnancy are particularly difficult to explore as interventions in pregnant women are not easily performed. Therefore, model...

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Autores principales:	Jenny L Sones, Christina C Yarborough, Valerie O'Besso, Alexander Lemenze, Nataki C Douglas
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e94c6771538d40a6894b1c5c57dbe0a3
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spelling	oai:doaj.org-article:e94c6771538d40a6894b1c5c57dbe0a32021-12-02T20:05:02ZGenotypic analysis of the female BPH/5 mouse, a model of superimposed preeclampsia.1932-620310.1371/journal.pone.0253453https://doaj.org/article/e94c6771538d40a6894b1c5c57dbe0a32021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253453https://doaj.org/toc/1932-6203Animal models that recapitulate human diseases and disorders are widely used to investigate etiology, diagnosis, and treatment of those conditions in people. Disorders during pregnancy are particularly difficult to explore as interventions in pregnant women are not easily performed. Therefore, models that allow for pre-conception investigations are advantageous for elucidating the mechanisms involved in adverse pregnancy outcomes that are responsible for both maternal and fetal morbidity, such as preeclampsia. The Blood Pressure High (BPH)/5 mouse model has been used extensively to study the pathogenesis of preeclampsia. The female BPH/5 mouse is obese with increased adiposity and borderline hypertension, both of which are exacerbated with pregnancy making it a model of superimposed preeclampsia. Thus, the BPH/5 model shares traits with a large majority of women with pre-existing conditions that predisposes them to preeclampsia. We sought to explore the genome of the BPH/5 female mouse and determine the genetic underpinnings that may contribute to preeclampsia-associated phenotypes in this model. Using a whole genome sequencing approach, we are the first to characterize the genetic mutations in BPH/5 female mice that make it unique from the closely related BPH/2 model and the normotensive background strain, C57Bl/6. We found the BPH/5 female mouse to be uniquely different from BPH/2 and C57Bl/6 mice with a genetically complex landscape. The majority of non-synonymous consequences within the coding region of BPH/5 females were missense mutations found most abundant on chromosome X when comparing BPH/5 and BPH/2, and on chromosome 8 when comparing BPH/5 to C57Bl/6. Genetic mutations in BPH/5 females largely belong to immune system-related processes, with overlap between BPH/5 and BPH/2 models. Further studies examining each gene mutation during pregnancy are warranted to determine key contributors to the BPH/5 preeclamptic-like phenotype and to identify genetic similarities to women that develop preeclampsia.Jenny L SonesChristina C YarboroughValerie O'BessoAlexander LemenzeNataki C DouglasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0253453 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jenny L Sones Christina C Yarborough Valerie O'Besso Alexander Lemenze Nataki C Douglas Genotypic analysis of the female BPH/5 mouse, a model of superimposed preeclampsia.
description	Animal models that recapitulate human diseases and disorders are widely used to investigate etiology, diagnosis, and treatment of those conditions in people. Disorders during pregnancy are particularly difficult to explore as interventions in pregnant women are not easily performed. Therefore, models that allow for pre-conception investigations are advantageous for elucidating the mechanisms involved in adverse pregnancy outcomes that are responsible for both maternal and fetal morbidity, such as preeclampsia. The Blood Pressure High (BPH)/5 mouse model has been used extensively to study the pathogenesis of preeclampsia. The female BPH/5 mouse is obese with increased adiposity and borderline hypertension, both of which are exacerbated with pregnancy making it a model of superimposed preeclampsia. Thus, the BPH/5 model shares traits with a large majority of women with pre-existing conditions that predisposes them to preeclampsia. We sought to explore the genome of the BPH/5 female mouse and determine the genetic underpinnings that may contribute to preeclampsia-associated phenotypes in this model. Using a whole genome sequencing approach, we are the first to characterize the genetic mutations in BPH/5 female mice that make it unique from the closely related BPH/2 model and the normotensive background strain, C57Bl/6. We found the BPH/5 female mouse to be uniquely different from BPH/2 and C57Bl/6 mice with a genetically complex landscape. The majority of non-synonymous consequences within the coding region of BPH/5 females were missense mutations found most abundant on chromosome X when comparing BPH/5 and BPH/2, and on chromosome 8 when comparing BPH/5 to C57Bl/6. Genetic mutations in BPH/5 females largely belong to immune system-related processes, with overlap between BPH/5 and BPH/2 models. Further studies examining each gene mutation during pregnancy are warranted to determine key contributors to the BPH/5 preeclamptic-like phenotype and to identify genetic similarities to women that develop preeclampsia.
format	article
author	Jenny L Sones Christina C Yarborough Valerie O'Besso Alexander Lemenze Nataki C Douglas
author_facet	Jenny L Sones Christina C Yarborough Valerie O'Besso Alexander Lemenze Nataki C Douglas
author_sort	Jenny L Sones
title	Genotypic analysis of the female BPH/5 mouse, a model of superimposed preeclampsia.
title_short	Genotypic analysis of the female BPH/5 mouse, a model of superimposed preeclampsia.
title_full	Genotypic analysis of the female BPH/5 mouse, a model of superimposed preeclampsia.
title_fullStr	Genotypic analysis of the female BPH/5 mouse, a model of superimposed preeclampsia.
title_full_unstemmed	Genotypic analysis of the female BPH/5 mouse, a model of superimposed preeclampsia.
title_sort	genotypic analysis of the female bph/5 mouse, a model of superimposed preeclampsia.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/e94c6771538d40a6894b1c5c57dbe0a3
work_keys_str_mv	AT jennylsones genotypicanalysisofthefemalebph5mouseamodelofsuperimposedpreeclampsia AT christinacyarborough genotypicanalysisofthefemalebph5mouseamodelofsuperimposedpreeclampsia AT valerieobesso genotypicanalysisofthefemalebph5mouseamodelofsuperimposedpreeclampsia AT alexanderlemenze genotypicanalysisofthefemalebph5mouseamodelofsuperimposedpreeclampsia AT natakicdouglas genotypicanalysisofthefemalebph5mouseamodelofsuperimposedpreeclampsia
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Genotypic analysis of the female BPH/5 mouse, a model of superimposed preeclampsia.

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