Funding Research for Treatments and a Cure

Understanding Ube3a Isoforms
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Dr. Ype Elgersma Dr. Ype Elgersma Erasmus MC, Rotterdam, The Netherlands

Understanding Ube3a Isoforms


The UBE3A protein has two variants called isoforms. This information has been known for some time, but only recently, research discovered that these two isoforms of UBE3A travel to different locations in the brain. The research team is applying this new knowledge to understand the basis of Angelman syndrome.

In typically developing humans, one of the UBE3A isoforms travels to the synapse, where neurons intersect in the brain and are told what to do. With the recent discovery, we now know the other UBE3A isoform goes to the nucleus of the neuron, where DNA is located.

These two isoforms work together for normal brain functionality. In individuals with Angelman syndrome, we know that UBE3A is not functioning properly (or entirely absent), but we do not know which isoform of Ube3a is responsible for causing Angelman syndrome, if not both.

Using this new knowledge, the research team will evaluate two types of mice: one missing the synapse isoform but keeping the nucleus isoform, and another missing the nucleus isoform but keeping the synapse isoform. This approach allows the team to research how each isoform impacts the mice, possibly shedding light on the importance of each isoform’s function.

This research is important because it will potentially:

  • Identify the importance of UBE3A isoforms in Angelman syndrome brain development.
  • Determine if the synapse isoform and/or if the nucleus isoform has greater impact on brain development, helping future research narrow its focus on which isoform is most important.