If biologists have learned anything over the past decade, it is how similar all mammals are at the genetic level. 95% of the genes found in mice are also found in humans, and we even share a significant amount of genes and genetic circuitries with creatures as different as fruit flies or puffer fish. This might not come as much of a surprise to physiologists who have long used animals to learn about basic mechanisms in organ function that are shared across vertebrates or mammals, but the extent of overlap is still impressive to most.

In many areas of biomedical research, rats or mice are the animal model of choice. And while most researchers are aware that mice are not just furry little humans that walk on all fours, some fundamental differences surprise even experts. Among 10 scientists who identify themselves as mouse geneticists, only one was aware that mice (and in fact all rodents) lack a very fundamental behavior: they do not vomit.

While that in itself raises all sorts of interesting questions (for example about the evolution of vomiting, and its advantages and disadvantages for the survival of a species), it poses a very specific problem when one tries to use rodents to study a drug with side effects that include nausea and emesis (the medical term for vomiting).

Annette Robichaud and colleagues at Merck Frosst Centre for Therapeutic Research in Montreal, Quebec, have faced this problem while developing drugs that inhibit a class of enzymes called class 4 phosphodiesterases, or PDE4s. PDE4 inhibitors have promise for the treatment of airway inflammatory diseases such as asthma, but their therapeutic potential has been limited by side effects of nausea and emesis. These side effects are thought to be caused by inhibition of PDE4s outside the airways. The PDE4 subfamily is composed of 4 subtypes that are present in overlapping but distinct tissues of the body, and the hope is that it might be possible to develop subtype-specific inhib
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Contact: Brooke Grindlinger
science_editor@the-jci.org
212-342-9006
Journal of Clinical Investigation
2-Oct-2002

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