Drosophila model

Liu et al., (2013) used a homologous recombination strategy to replace exon 1 of the the Drosophila FLCN homologue, DBHD, with a white gene marker, resulting in a null DBHD allele. The mutant phenotype was only evident in flies homozygous for the DBHD exon 1 deletion. DBHD-null flies did not develop into adulthood, but remained in a small, early larval form for an extended period of up to three weeks, as opposed to three days in wildtype and heterozygous flies. This starvation phenotype was partially rescued by human FLCN, suggesting that the two proteins have some overlapping function. Dietary leucine also partially rescued the phenotype, allowing flies to reach the larval stage, although they still died during metamorphosis, suggesting that reduced mTOR signalling was partially responsible for this phenotype.