Standardised imaging pipeline for phenotyping mouse laterality defects and associated heart malformations, at multiple scales and multiple stages
Laterality defects are developmental disorders resulting from aberrant left/right patterning. In the most severe cases, such as in heterotaxy, they are associated with complex malformations of the heart. Advances in understanding the underlying physiopathological mechanisms have been hindered by the...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2019-07-01
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| Series: | Disease Models & Mechanisms |
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| Online Access: | http://dmm.biologists.org/content/12/7/dmm038356 |
| _version_ | 1828870199986618368 |
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| author | Audrey Desgrange Johanna Lokmer Carmen Marchiol Lucile Houyel Sigolène M. Meilhac |
| author_facet | Audrey Desgrange Johanna Lokmer Carmen Marchiol Lucile Houyel Sigolène M. Meilhac |
| author_sort | Audrey Desgrange |
| collection | DOAJ |
| description | Laterality defects are developmental disorders resulting from aberrant left/right patterning. In the most severe cases, such as in heterotaxy, they are associated with complex malformations of the heart. Advances in understanding the underlying physiopathological mechanisms have been hindered by the lack of a standardised and exhaustive procedure in mouse models for phenotyping left/right asymmetries of all visceral organs. Here, we have developed a multimodality imaging pipeline, which combines non-invasive micro-ultrasound imaging, micro-computed tomography (micro-CT) and high-resolution episcopic microscopy (HREM) to acquire 3D images at multiple stages of development and at multiple scales. On the basis of the position in the uterine horns, we track in a single individual, the progression of organ asymmetry, the situs of all visceral organs in the thoracic or abdominal environment, and the fine anatomical left/right asymmetries of cardiac segments. We provide reference anatomical images and organ reconstructions in the mouse, and discuss differences with humans. This standardised pipeline, which we validated in a mouse model of heterotaxy, offers a fast and easy-to-implement framework. The extensive 3D phenotyping of organ asymmetry in the mouse uses the clinical nomenclature for direct comparison with patient phenotypes. It is compatible with automated and quantitative image analyses, which is essential to compare mutant phenotypes with incomplete penetrance and to gain mechanistic insight into laterality defects. |
| first_indexed | 2024-12-13T06:07:29Z |
| format | Article |
| id | doaj.art-b4b6f473277c4946941bd4a30584a194 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-13T06:07:29Z |
| publishDate | 2019-07-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-b4b6f473277c4946941bd4a30584a1942022-12-21T23:57:12ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112019-07-0112710.1242/dmm.038356038356Standardised imaging pipeline for phenotyping mouse laterality defects and associated heart malformations, at multiple scales and multiple stagesAudrey Desgrange0Johanna Lokmer1Carmen Marchiol2Lucile Houyel3Sigolène M. Meilhac4 Imagine-Institut Pasteur, Laboratory of Heart Morphogenesis, 75015 Paris, France Imagine-Institut Pasteur, Laboratory of Heart Morphogenesis, 75015 Paris, France Université Paris Descartes, Sorbonne Paris-Cité, 75006 Paris, France Université Paris Descartes, Sorbonne Paris-Cité, 75006 Paris, France Imagine-Institut Pasteur, Laboratory of Heart Morphogenesis, 75015 Paris, France Laterality defects are developmental disorders resulting from aberrant left/right patterning. In the most severe cases, such as in heterotaxy, they are associated with complex malformations of the heart. Advances in understanding the underlying physiopathological mechanisms have been hindered by the lack of a standardised and exhaustive procedure in mouse models for phenotyping left/right asymmetries of all visceral organs. Here, we have developed a multimodality imaging pipeline, which combines non-invasive micro-ultrasound imaging, micro-computed tomography (micro-CT) and high-resolution episcopic microscopy (HREM) to acquire 3D images at multiple stages of development and at multiple scales. On the basis of the position in the uterine horns, we track in a single individual, the progression of organ asymmetry, the situs of all visceral organs in the thoracic or abdominal environment, and the fine anatomical left/right asymmetries of cardiac segments. We provide reference anatomical images and organ reconstructions in the mouse, and discuss differences with humans. This standardised pipeline, which we validated in a mouse model of heterotaxy, offers a fast and easy-to-implement framework. The extensive 3D phenotyping of organ asymmetry in the mouse uses the clinical nomenclature for direct comparison with patient phenotypes. It is compatible with automated and quantitative image analyses, which is essential to compare mutant phenotypes with incomplete penetrance and to gain mechanistic insight into laterality defects.http://dmm.biologists.org/content/12/7/dmm038356Laterality defectsHeterotaxyCongenital heart defectsSitus3D imagingLeft-right asymmetry |
| spellingShingle | Audrey Desgrange Johanna Lokmer Carmen Marchiol Lucile Houyel Sigolène M. Meilhac Standardised imaging pipeline for phenotyping mouse laterality defects and associated heart malformations, at multiple scales and multiple stages Disease Models & Mechanisms Laterality defects Heterotaxy Congenital heart defects Situs 3D imaging Left-right asymmetry |
| title | Standardised imaging pipeline for phenotyping mouse laterality defects and associated heart malformations, at multiple scales and multiple stages |
| title_full | Standardised imaging pipeline for phenotyping mouse laterality defects and associated heart malformations, at multiple scales and multiple stages |
| title_fullStr | Standardised imaging pipeline for phenotyping mouse laterality defects and associated heart malformations, at multiple scales and multiple stages |
| title_full_unstemmed | Standardised imaging pipeline for phenotyping mouse laterality defects and associated heart malformations, at multiple scales and multiple stages |
| title_short | Standardised imaging pipeline for phenotyping mouse laterality defects and associated heart malformations, at multiple scales and multiple stages |
| title_sort | standardised imaging pipeline for phenotyping mouse laterality defects and associated heart malformations at multiple scales and multiple stages |
| topic | Laterality defects Heterotaxy Congenital heart defects Situs 3D imaging Left-right asymmetry |
| url | http://dmm.biologists.org/content/12/7/dmm038356 |
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