A mouse model to assess genetic therapies for Prader-Willi syndrome (Year 2)

Funding Summary

Dr. Resnick and his team have developed a mouse model of PWS that allows precise activation/replacement of the missing PWS genes at different times during development and in different tissues. In this second year of funding, they will work to reestablish gene expression and determine the effects on the potential reversal of traits. As time permits, we will also re-establish PWS gene expression at various times in order to determine how late in pre or postnatal development Snord116 expression must be restored to have a beneficial effect.

Lay Abstract

Individuals with Prader-Willi syndrome lack the activity of several genes that are normally expressed from only the paternally inherited copy of chromosome 15. Genetic therapies often seek to re-establish expression of the missing gene products. In some syndromes, the missing gene products are necessary only transiently, even though the gene normally continues to be expressed. The proposed research seeks to determine whether gene replacement therapies can be of value in the treatment of PWS, and if so, when the missing gene products must be re-established to have beneficial effect. We have generated a novel mouse mutant that undergoes development in the near absence of Snord116, a PWS gene strongly implicated in many traits. Pups inheriting this mutation exhibit growth retardation, a trait also seen in pups deleted for the Snord116. The mutation was constructed so that the absent gene products can be readily turned back on at predetermined times either before or after birth. Reversal of traits following reestablishment of gene expression will indicate that genetic therapies can be of value. As time permits, we will also re-establish PWS gene expression at various times in order to determine how late in pre or postnatal development Snord116 expression must be restored to have a beneficial effect. We anticipate that these results can inform PWS gene therapy trials as to when and where PWS genes should be expressed to have therapeutic value.

Funded Year:

2020

Awarded to:

James Resnick, Ph.D

Amount:

$97,909

Institution:

University of Florida

Researcher:

James Resnick, Ph.D

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