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A mouse model of hypoplastic left heart syndrome demonstrating left heart hypoplasia and retrograde aortic arch flow

A mouse model of hypoplastic left heart syndrome demonstrating left heart hypoplasia and retrograde aortic arch flow

Authors :
Anum Rahman
Taylor DeYoung
Lindsay S. Cahill
Yohan Yee
Sarah K. Debebe
Owen Botelho
Mike Seed
Rajiv R. Chaturvedi
John G. Sled
Source :
Disease Models & Mechanisms, Vol 14, Iss 11 (2021)
Publication Year :
2021
Publisher :
The Company of Biologists, 2021.

Abstract

In hypoplastic left heart syndrome (HLHS), the mechanisms leading to left heart hypoplasia and their associated fetal abnormalities are largely unknown. Current animal models have limited utility in resolving these questions as they either do not fully reproduce the cardiac phenotype, do not survive to term and/or have very low disease penetrance. Here, we report the development of a surgically induced mouse model of HLHS that overcomes these limitations. Briefly, we microinjected the fetal left atrium of embryonic day (E)14.5 mice with an embolizing agent under high-frequency ultrasound guidance, which partially blocks blood flow into the left heart and induces hypoplasia. At term (E18.5), all positively embolized mice exhibit retrograde aortic arch flow, non-apex-forming left ventricles and hypoplastic ascending aortas. We thus report the development of the first mouse model of isolated HLHS with a fully penetrant cardiac phenotype and survival to term. Our method allows for the interrogation of previously intractable questions, such as determining the mechanisms of cardiac hypoplasia and fetal abnormalities observed in HLHS, as well as testing of mechanism-based therapies, which are urgently lacking.

Details

Language :
English
ISSN :
17548403 and 17548411
Volume :
14
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Disease Models & Mechanisms
Publication Type :
Academic Journal
Accession number :
edsdoj.00f6009b077645dcb36ca642e314f5c0
Document Type :
article
Full Text :
https://doi.org/10.1242/dmm.049077