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Developmental Biology Boot Camp

CDH Disease Models

The first description of CDH was in 1575 by the skilled French surgeon, Ambroise Pare.
The first description of CDH was in 1575 by the skilled French surgeon, Ambroise Pare.

 

How do we study CDH?

This question has plagued researchers since the first description of CDH in the 1500’s. And yet, despite intervening treatments spanning more than a century , there are currently no effective interventions for more severe presentations. In fact, even optimistic estimates place the survival rate of type D CDH at less than 60% (see: severity).

Classically, animal models to study CDH fall into three categories. One is surgical models, in which an incision is made in the developing embryo to mimic hernial defect. These have classically been used in both lambs and rabbits.  Two is pharmacological models, in which a teratogenic drug is administered. Perhaps most notable is a study using the herbicide nitrofen in mice. Three is congenital models, whereby a congenital defect is discovered in a specific animal population.

Proposed experiment to pharmacologically model CDH using Xenopus eggs.
Proposed experiment to pharmacologically model CDH using Xenopus eggs.

What about Xenopus as a disease model for CDH?

Frogs differ from humans in that they do not have a diaphragm. Instead, these animals respire i) through the skin while underwater, ii) readily through a lining on the mouth surface, and also iii) by breathing much like humans, pulling air into the nostrils by expanding the throat, then forcing air into the lungs by contracting the mouth floor. As such, Xenopus appears non-ideal for modeling CDH.

It may be that the most effective approach to model CDH in Xenopus is to induce lung hypoplasia pharmacologically with a teratogenic compound like nitrofen, which has been used previously to model CDH in rat explants of lung tissue. This could be performed by soaking embryos in the compound at varying concentrations and for varying amounts of time to until milder to more severe phenotypes can be achieved. Then, development of Xenopus animals can be monitored for malformations in lung development mirroring hypoplasia observed in CDH.