Relevance to Autism

The gene product of TOP3B, TOP3b, was recently shown to interact with FMRP, the protein deficient in Fragile X syndrome, a syndromic form of autism, and that this interaction was abolished by a disease-associated mutation of FMRP (Xu et al., 2013). Furthermore, this report demonstrated that Top3b binds mRNAs encoded by genes with neuronal functions linked to schizophrenia and autism, and that synapse formation was defective in both TOP3B mutant files and mice. A subsequent report showed that enrichment of a rare chromosome 22q11.22 deletion in a Northern Finnish isolate allowed for the detection of association between the TOP3B gene and both schizophrenia and intellectual disability (Stoll et al., 2013).

Molecular Function

This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus relaxing the supercoils and altering the topology of DNA. The enzyme interacts with DNA helicase SGS1 and plays a role in DNA recombination, cellular aging and maintenance of genome stability. Recently, this enzyme was shown to also have RNA topoisomerase activity (Xu et al., 2013; Stoll et al., 2013).

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Model Summary

Top3Beta KO mice have abnormal synapse formation and reduced synaptophysin in pre and post synaptic vesicles.

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