[Zbrafish] thalidomide teratogenicity

ZFIN Admin via zbrafish%40net.bio.net (by zfinadmin from gmail.com)
Thu Apr 22 11:04:07 EST 2010

Dear zebrafish researchers,

As you know, zebrafish has long been contributing largely to medical
research. Its highly conserved synteny makes us easy to investigate
molecular mechanisms of drug efficacy, as well as its side-effect.

Today, zebrafish research identified primary target of thalidomide
teratogenicity. Over half a century ago, thalidomide was widely used
as a treatment for morning sickness. But unfortunately, by its side-
effects, some 10,000 babies have been born with birth defects, such as
malformations of the ear and limbs.

Now our team have identified a protein called Cereblon or CRBN whose
binding to thalidomide contributes to the drug’s side-effects in limb
development (Science, 2010, 327, 1345). We engineered zebrafish to
express CRBN proteins that can’t bind thalidomide, and exposed to the
drug during development. The engineered fish did not show the severe
birth defects, reduction of otic vesicle's size and shortening of
pectoral fins those were seen in the control, untreated fish exposed
to the drug. This suggests that CRBN is a primary target of
thalidomide teratogenicity.

-Hideki Ando

We believe this study reveals a basis for thalidomide teratogenicity
and may contribute to the development of new thalidomide derivatives
without teratogenic activity.

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