Members of the solute carrier family 9 (SLC9A1–9) are connected to a spectrum of neurodevelopmental disorders. Mutations in SLC9A6 cause syndromic X-linked intellectual disability Christianson-type, with microcephaly, epilepsy, and ataxia, and shows phenotypic overlap with Angelman syndrome. Mutations in SLC9A9 causes autism with seizures, and variants in the gene are associated with Attention Deficit Hyperactivity Disorder-related deficits.
The Drosophila homolog of human SLC9A6 and SLC9A9 is Nhe3. The protein codes for a Na+/H+ hydrogen exchanger that is highly expressed in the brain. We have dissected Drosophila larvae to study the structure of synapses at the neuromuscular junction and dendritic branching of the class IV dorsal dendritic arborization C (ddaC) neurons. In addition we have performed behavioral characterization in adults, namely habituation and locomotor activity profiling.
We observe strong neurodevelopmental defects and behavioral aberrations, consistent with the neurodevelopmental defects observed in humans. We want to exploit this Drosophila model of early onset cognitive disorders to gain mechanistic insight in the neuronal defects and development clinical applications1.
Relevant review: 1van der Voet M, Nijhof B, Oortveld MA, Schenck A. Drosophila models of early onset cognitive disorders and their clinical applications. Neurosci Biobehav Rev. 2014 doi: 10.1016/j.neubiorev.2014.01.013.