Email this article 
Design of COMT-Knockout mouse as a preeclampsia mode
- Authors: Chirinskaite A.V.1, Fotina A.S.1, Markova E.V.1, Vishnyakova P.A.2,3, Poltavets A.S.2,3, Sopova J.V.1,4, Leonova E.I.1
-
Affiliations:
- Saint Petersburg State University
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov
- Рeoples’ Friendship University of Russia
- Saint Petersburg branch of Vavilov Institute of General Genetics
- Issue: Vol 20 (2022): Supplement
- Pages: 46-47
- Section: Genetically modified organism. The Нistory, Achivements, Social and Environmental Riscs
- URL: https://journals.eco-vector.com/ecolgenet/article/view/112358
- DOI: https://doi.org/10.17816/ecogen112358
- ID: 112358
Cite item
Full Text
Abstract
Preeclampsia is a multisystem pregnancy disorder that occurs after 20 weeks of gestation, leading to e.g. preterm labor. It is characterized by hypertension, proteinuria, edema, and multiple organ dysfunction. Up to 8% of pregnancies are complicated by preeclampsia, which is one of the most serious causes of maternal and perinatal mortality [1]. For research of pregnancy disorders and development of therapy for it, a mouse model can be used due of the fact that pregnancy development in mice, especially at early stages, is somewhat similar to human and is well-studied, in particular, in terms of molecular biology [2]. One of the possible options for creating mouse models of preeclampsia is considered to be a mutation in the COMT gene encoding сatechol-O-methyltransferase [3]. This enzyme plays an important role in the catecholamines conversion and it also catalyzes the O-methylation of hydroxyestradiol producing methoxyestradiol. COMT gene knockout results in a phenotype similar to preeclampsia with elevated blood pressure and proteinuria [3]. The previous model was obtained through classic transgenesis methods with Neomycin cassette insertion in the COMT locus potentially influencing the results of the experiments. The development of the genome editing systems and its active utilization at Saint Petersburg State University made it possible to obtain a COMT-KO mouse line using CRISPR/Cas9 technology which had not been done in Russia before. This model will allow to effectively study the development of preeclampsia and ways to prevent and treat it.
This work was supported by a Saint Petersburg State University grant for the development of scientific research (ID 92561695).
Full Text
Preeclampsia is a multisystem pregnancy disorder that occurs after 20 weeks of gestation, leading to e.g. preterm labor. It is characterized by hypertension, proteinuria, edema, and multiple organ dysfunction. Up to 8% of pregnancies are complicated by preeclampsia, which is one of the most serious causes of maternal and perinatal mortality [1]. For research of pregnancy disorders and development of therapy for it, a mouse model can be used due of the fact that pregnancy development in mice, especially at early stages, is somewhat similar to human and is well-studied, in particular, in terms of molecular biology [2]. One of the possible options for creating mouse models of preeclampsia is considered to be a mutation in the COMT gene encoding сatechol-O-methyltransferase [3]. This enzyme plays an important role in the catecholamines conversion and it also catalyzes the O-methylation of hydroxyestradiol producing methoxyestradiol. COMT gene knockout results in a phenotype similar to preeclampsia with elevated blood pressure and proteinuria [3]. The previous model was obtained through classic transgenesis methods with Neomycin cassette insertion in the COMT locus potentially influencing the results of the experiments. The development of the genome editing systems and its active utilization at Saint Petersburg State University made it possible to obtain a COMT-KO mouse line using CRISPR/Cas9 technology which had not been done in Russia before. This model will allow to effectively study the development of preeclampsia and ways to prevent and treat it.
This work was supported by a Saint Petersburg State University grant for the development of scientific research (ID 92561695).
About the authors
Angelina V. Chirinskaite
Saint Petersburg State University
Author for correspondence.
Email: ChirinskaiteA@yandex.ru
SPIN-code: 3689-0110
Junior Researcher, Center for Transgenesis and Genome Editing
Russian Federation, Saint PetersburgAleksandra S. Fotina
Saint Petersburg State University
Email: sfotina1801@gmail.com
Research Assistant, Center for Transgenesis and Genome Editing
Russian Federation, Saint PetersburgEkaterina V. Markova
Saint Petersburg State University
Email: st076326@student.spbu.ru
Research Assistant, Center for Transgenesis and Genome Editing
Russian Federation, Saint PetersburgPolina A. Vishnyakova
National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov; Рeoples’ Friendship University of Russia
Email: vpa2002@mail.ru
PhD, Senior Researcher, Laboratory of Regenerative Medicine; Histology Department, Medical Institute
Russian Federation, Moscow; MoscowAnastasiya S. Poltavets
National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov; Рeoples’ Friendship University of Russia
Email: A.poltavets@yandex.ru
Junior Researcher, Laboratory of Regenerative; Histology Department, Medical Institute
Russian Federation, Moscow; MoscowJulia V. Sopova
Saint Petersburg State University; Saint Petersburg branch of Vavilov Institute of General Genetics
Email: sopova@hotmail.com
SPIN-code: 6019-1547
PhD, Leading Researcher, Center for transgenesis and genome editing; Researcher, Laboratory of Amyloid Biology; Researcher, Laboratory of Genetic Models of Human Diseases
Russian Federation, Saint Petersburg; Saint PetersburgElena I. Leonova
Saint Petersburg State University
Email: 1102.elena@gmail.com
SPIN-code: 2573-1759
PhD, Head, Center for Transgenesis and Genome Editing
Russian Federation, Saint PetersburgReferences
- Sibai BM. Preeclampsia As a Cause of Preterm and Late Preterm (Near-Term) Births. Semin Perinatol. 2006;30(1):16–19. doi: 10.1053/j.semperi.2006.01.008
- Wu SP, Emery OM, DeMayo FJ. Molecular Studies on Pregnancy with Mouse Models. Curr Opin Physiol. 2020;13:123–127. doi: 10.1016/j.cophys.2019.10.018
- Kanasaki K, Palmsten K, Sugimoto H, et al. Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia. Nature. 2008;453(7198):1117–1121. doi: 10.1038/nature06951
Supplementary files
