A spectrum of tracheo-esophageal malformations is seen in humans: esophageal atresia, tracheal agenesis and laryngotracheo-esophageal clefts. They are thought to share a common but unknown aetiology. These birth defects are frequently associated with other VACTERL anomalies. The adriamycin rat model (ARM) has proved to be a valuable model of the VACTERL anomalies, illustrating the dysmorphogenesis of esophageal atresia and tracheal agenesis. As organogenesis relies on temporaspatially co-ordinated signalling systems, the next step would be to study the molecular pathogenesis of tracheo-esophageal malformations. However, the mouse is the foremost mammal studied by developmental biologists, offering an expanding wealth of knowledge and scientific research techniques with which to investigate these anomalies. A limited dose response analysis of the teratogenicity of adriamycin in the mouse has identified a dose and timing of injections that produced tracheo-esophageal malformations and other VACTERL anomalies. A clear account of the types and variability of the tracheo-esophageal malformations produced by this dose is essential in order to be able to plan and interpret any future investigations of early gestation fetuses. CBA/Ca mice were accurately time-mated 10. Nine dams received intraperitoneal injections of adriamycin (6 mg/kg) and one control dam received saline injections, on days 7 and 8. Fetuses were harvested on day 18, near term. Tracheo-esophageal malformations were examined by dissecting microscope and serial transverse sections. Results are reported in the standard teratological manner as mean percentage per litter (±SEM). The resorption rate of the adriamycin treated fetuses was 50.4%. There were 29 adriamycin treated fetuses for inspection. Tracheo-esophageal malformations were found in 29.2% (±10.3), affecting five out of nine litters. esophageal atresia occurred in 15.6% (±8.1), laryngotracheo-esophageal cleft in 10.4% (±7) and tracheal agenesis in 3.1% (±3.1). All of these malformations occurred with a tracheo-oesophageal fistula. Unlike the ARM, the AMM can produce fetuses with complete laryngotracheo-esophageal cleft as well as esophageal atresia or tracheal agenesis. Their occurrence was found to be reproducible but variable. These are important considerations when planning and interpreting experiments using this model.

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