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A missense mutation of ErbB2 produces a novel mouse model of stillbirth associated with a cardiac abnormality but lacking abnormalities of placental structure.
- Source :
-
PloS one [PLoS One] 2020 Jun 03; Vol. 15 (6), pp. e0233007. Date of Electronic Publication: 2020 Jun 03 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Background: In humans, stillbirth describes the death of a fetus before birth after 28 weeks gestation, and accounts for approximately 2.6 million deaths worldwide annually. In high-income countries, up to half of stillbirths have an unknown cause and are described as "unexplained stillbirths"; this lack of understanding impairs efforts to prevent stillbirth. There are also few animal models of stillbirth, but those that have been described usually have significant placental abnormalities. This study describes a novel mutant murine model of fetal death with atrial conduction block due to an ErbB2 missense mutation which is not associated with abnormal placental morphology.<br />Methods: Phenotypic characterisation and histological analysis of the mutant mouse model was conducted. The mRNA distribution of the early cardiomyocyte marker Nkx2-5 was assessed via in situ hybridisation. Cardiac structure was quantified and cellular morphology evaluated by electron microscopy. Immunostaining was employed to quantify placental structure and cell characteristics on matched heterozygous and homozygous mutant placental samples.<br />Results: There were no structural abnormalities observed in hearts of mutant embryos. Comparable Nkx2-5 expression was observed in hearts of mutants and controls, suggesting normal cardiac specification. Additionally, there was no significant difference in the weight, placenta dimensions, giant cell characteristics, labyrinth tissue composition, levels of apoptosis, proliferation or vascularisation between placentas of homozygous mutant mice and controls.<br />Conclusion: Embryonic lethality in the ErbB2 homozygous mutant mouse cannot be attributed to placental pathology. As such, we conclude the ErbB2M802R mutant is a model of stillbirth with a non-placental cause of death. The mechanism of the atrial block resulting from ErbB2 mutation and its role in embryonic death is still unclear. Studying this mutant mouse model could identify candidate genes involved in stillbirth associated with structural or functional cardiac defects.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Disease Models, Animal
Female
Heart Block congenital
Heart Block genetics
Heart Block metabolism
Heart Block pathology
Heart Defects, Congenital metabolism
Heart Defects, Congenital pathology
Heterozygote
Homeobox Protein Nkx-2.5 genetics
Homozygote
Humans
Mice
Mice, Mutant Strains
Myocardium metabolism
Myocardium pathology
Placenta abnormalities
Placenta pathology
Pregnancy
RNA, Messenger genetics
RNA, Messenger metabolism
Heart Defects, Congenital genetics
Mutation, Missense
Receptor, ErbB-2 genetics
Stillbirth genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 15
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 32492036
- Full Text :
- https://doi.org/10.1371/journal.pone.0233007