Characterization of the congenital diaphragmatic hernia model in C57BL/6J fetal mice: a step toward lineage tracing experiments.

Animal model C57BL/6J Lineage tracing Lung development Maturation Pulmonary hypertension Pulmonary hypoplasia Vascularization

Journal

Pediatric surgery international
ISSN: 1437-9813
Titre abrégé: Pediatr Surg Int
Pays: Germany
ID NLM: 8609169

Informations de publication

Date de publication:
20 Nov 2023
Historique:
accepted: 25 10 2023
medline: 21 11 2023
pubmed: 20 11 2023
entrez: 19 11 2023
Statut: epublish

Résumé

Lineage tracing is key to study the fate of individual cells and their progeny especially in developmental biology. To conduct these studies, we aimed to establish a reproducible model of CDH in the most commonly used genetic background strain that is C57BL/6J mice. CDH was induced in C57BL/6J dams by maternal administration of nitrofen + bisdiamine at E8.5. Fetuses from olive oil-gavaged mothers served as controls. Lungs from CDH and control fetuses were compared for (1) growth via radial airspace count (RAC), mean linear intercept (MLI) and gene expression for Fgf10, Nrp1, and Ctnnb1; (2) maturation (Pdpn, Spc, Ager, Abca3, Eln, Acta2, Pdgfra) via gene and protein expression; (3) vascularization via gene and protein expression (CD31, Vegfa, Vegfr1/2, Epas1, Enos). unpaired t-test or Mann-Whitney test. Nitrofen + bisdiamine administration resulted in 36% left-sided CDH (31% mortality). CDH fetuses had hypoplastic lungs and impaired growth (lower RAC, higher MLI, lower Fgf10, Nrp1, Ctnnb1), maturation (decreased Pdpn, Ager, Eln gene expression), and vascularization (decreased Cd31, Vegfr1/2; Epas1 and Enos). Lower protein expression was confirmed for PDPN, ELN and CD31. Modeling CDH in C57BL/6J mouse fetuses is effective in reproducing the classical CDH hallmarks. This model will be critical for lineage tracing experiments.

Identifiants

pubmed: 37981587
doi: 10.1007/s00383-023-05583-y
pii: 10.1007/s00383-023-05583-y
doi:

Substances chimiques

nitrofen N71UYG034A
Transcription Factors 0
nitrophen 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

296

Subventions

Organisme : CIHR
ID : 175300
Pays : Canada

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Références

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Auteurs

Fabian Doktor (F)

Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, M5G 0A4, Canada.
Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, M5G 1X8, Canada.
Department of Pediatric Surgery, University of Leipzig, 04109, Leipzig, Germany.

Rebeca Lopes Figueira (RL)

Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, M5G 0A4, Canada.
Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, M5G 1X8, Canada.

Kasra Khalaj (K)

Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, M5G 0A4, Canada.
Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, M5G 1X8, Canada.

Aizah Ijaz (A)

Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, M5G 0A4, Canada.
Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, M5G 1X8, Canada.

Martin Lacher (M)

Department of Pediatric Surgery, University of Leipzig, 04109, Leipzig, Germany.

Matisse Blundell (M)

Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, M5G 0A4, Canada.
Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, M5G 1X8, Canada.

Lina Antounians (L)

Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, M5G 0A4, Canada.
Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, M5G 1X8, Canada.

Augusto Zani (A)

Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, M5G 0A4, Canada. augusto.zani@sickkids.ca.
Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, M5G 1X8, Canada. augusto.zani@sickkids.ca.
Department of Surgery, University of Toronto, Toronto, M5T 1P5, Canada. augusto.zani@sickkids.ca.

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