A mouse model of hypoplastic left heart syndrome demonstrating left heart hypoplasia and retrograde aortic arch flow
| Autor: | Taylor DeYoung, Sarah K. Debebe, Rajiv Chaturvedi, Lindsay S. Cahill, Owen Botelho, Mike Seed, Yohan Yee, Anum Rahman, John G. Sled |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Aortic arch
medicine.medical_specialty Heart Ventricles Neuroscience (miscellaneous) Medicine (miscellaneous) Aorta Thoracic 030204 cardiovascular system & hematology General Biochemistry Genetics and Molecular Biology Hypoplastic left heart syndrome Mouse model 03 medical and health sciences Mice 0302 clinical medicine Fetus Magnetic resonance imaging Immunology and Microbiology (miscellaneous) Internal medicine medicine.artery Ultrasound medicine Pathology RB1-214 Developmental Disorders Animals Resource Article 030304 developmental biology Congenital heart disease 0303 health sciences medicine.diagnostic_test business.industry Hemodynamics Blood flow medicine.disease Penetrance Hypoplasia 3. Good health Ultrasound guidance Cardiology Medicine business |
| Zdroj: | Disease Models & Mechanisms article-version (VoR) Version of Record Disease Models & Mechanisms, Vol 14, Iss 11 (2021) |
| ISSN: | 1754-8411 1754-8403 |
| Popis: | 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. Summary: We report the first mouse model of isolated hypoplastic left heart syndrome (HLHS), allowing for the investigation of abnormal cardiac, brain and placental development that is implicated in HLHS. |
| Databáze: | OpenAIRE |
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