Adriamycin mouse model: a variable but reproducible model of tracheo-oesophageal malformations

Dawrant, Michael J.; Giles, Shay; Bannigan, John; Puri, Prem

doi:10.1007/s00383-006-1847-9

Cited by 13 publications

(8 citation statements)

References 19 publications

(19 reference statements)

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“…The Adriamycin rat model, which has also been adapted to the mouse, is a teratogenic model of EA/TEF (Diez-Pardo et al, 1996;Dawrant et al, 2007). Adriamycin is a glycosidic anthracycline antibiotic, which is used in chemotherapy.…”

Section: Experimental Teratogenic Modelmentioning

confidence: 99%

Genetic and environmental factors in the etiology of esophageal atresia and/or tracheoesophageal fistula: An overview of the current concepts

Felix¹,

Jong²,

Torfs³

et al. 2009

Birth Defects Research

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Esophageal atresia and/or tracheoesophageal fistula (EA/TEF) are severe congenital anomalies. Although recent years have brought significant improvement in clinical treatment, our understanding of the etiology of these defects is lagging. Many genes and genetic pathways have been implicated in the development of EA/TEF, but only a few genes have been shown to be involved in humans, in animals, or in both. Extrapolating data from animal models to humans is not always straightforward. Environmental factors may also carry a risk, but the mechanisms are yet to be elucidated. This review gives an overview of the current state of knowledge about both genetic and environmental risk factors in the etiology of EA/TEF.

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Section: Experimental Teratogenic Modelmentioning

confidence: 99%

Genetic and environmental factors in the etiology of esophageal atresia and/or tracheoesophageal fistula: An overview of the current concepts

Felix¹,

Jong²,

Torfs³

et al. 2009

Birth Defects Research

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“…The mouse is the foremost mammalian model of development, offering an expanding wealth of genetic and molecular knowledge and scientific research techniques. Our group has confirmed that the Adriamycin mouse model (AMM) produces a spectrum of tracheo-oesophageal malformations [5,6].…”

Section: Introductionmentioning

confidence: 54%

Visualizing expression patterns of Shh and Foxf1 genes in the foregut and lung buds by optical projection tomography

et al. 2007

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Congenital malformations of the foregut are common in humans. The respiratory and digestive tubes are both derived by division of the foregut primordium. Sonic hedgehog (Shh) and Fork head box F1 (Foxf1) genes encode regulatory molecules that play a pivotal role in gut and lung morphogenesis and are therefore important candidate genes to be examined in models of foregut developmental disruption. Optical projection tomography (OPT) is a new, rapid and non-invasive technique for three-dimensional (3D) imaging of small biological tissue specimens that allows visualization of the tissue distribution of RNA in developing organs while also recording morphology. To explore the application of OPT in this context, we visualized Shh and Foxf1 gene expression patterns in the mouse foregut and lung buds at several stages of development. Time-mated CBA/Ca mice were harvested on embryonic days 9-12. The embryos were stained following whole mount in situ hybridization with labelled RNA probes to detect Shh and Foxf1 transcripts at each stage. The embryos were scanned by OPT to obtain 3D representations of gene expression domains in the context of the changing morphology of the embryo. OPT analysis of Shh and Foxf1 expression in the foregut and lung buds revealed extra details of the patterns not previously reported, particularly in the case of Foxf1 where gene expression was revealed in a changing pattern in the mesenchyme around the developing lung. Shh expression was also revealed in the epithelium of the lung bud itself. Both genes were detected in complementary patterns in the developing bronchi as late as E12, showing successful penetration of molecular probes and imaging at later stages. OPT is a valuable tool for revealing gene expression in an anatomical context even in internal tissues like the foregut and lung buds across stages of development, at least until E12. This provides the possibility of visualizing altered gene expression in an in vivo context in genetic or teratogenic models of congenital malformations.

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“…Dawrant et al [53] reported that the administration of an increased dose of Adriamycin of 6 mg/kg induced foregut and notochord anomalies in 64% of exposed embryos. The notochord was identical to that seen in the ARM, in that similarly in the mouse the administration of Adriamycin seems to cause a prolonged and abnormal adhesion between the endoderm and notochord (Figs.…”

Section: The Mouse Modelmentioning

confidence: 98%

The Adriamycin rat/mouse model and its importance to the paediatric surgeon

et al. 2007

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The teratogenic effect of Adriamycin (doxorubicin) in the rat model, and more recently in the mouse, has provided paediatric surgeons with a reliable, easily reproducible method of studying the embryology and molecular biology for a range of complex congenital anomalies. Concomitantly these animal models have stimulated interest among embryologists for the effect on the notochord, shedding more light on the important organizational role of this structure in the developing embryo. Finally, as more is learnt of the pathogenesis of the various malformations induced by Adriamycin, future therapeutic interventions involving gene therapy, drugs or surgery may arise. This article reviews the establishment of the Adriamycin rat and mouse models, examines their impact on various congenital malformations, and suggests targets for further research.

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Adriamycin mouse model: a variable but reproducible model of tracheo-oesophageal malformations

Cited by 13 publications

References 19 publications

Genetic and environmental factors in the etiology of esophageal atresia and/or tracheoesophageal fistula: An overview of the current concepts

Genetic and environmental factors in the etiology of esophageal atresia and/or tracheoesophageal fistula: An overview of the current concepts

Visualizing expression patterns of Shh and Foxf1 genes in the foregut and lung buds by optical projection tomography

The Adriamycin rat/mouse model and its importance to the paediatric surgeon

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