New fly model of Pitt-Hopkins syndrome (PTHS)--human TCF4 can rescue mutations in Drosophila ortholog daugherless

Tamberg L, Sepp M, Timmusk T, Palgi M. Introducing Pitt-Hopkins syndrome-associated mutations of TCF4 to Drosophila daughterless. Biol Open. 2015 Nov 30. PMID: 26621827.

From the abstract: "Pitt-Hopkins syndrome (PTHS) is caused by haploinsufficiency of Transcription factor 4 (TCF4), one of the three human class I basic helix-loop-helix transcription factors called E-proteins. Drosophila has a single E-protein, Daughterless (Da), homologous to all three mammalian counterparts. ... human TCF4 can rescue Da deficiency during fruit fly nervous system development. ... We generated da transgenic fruit fly strains with corresponding missense mutations R578H, R580W, R582P and A614V found in TCF4 of PTHS patients and studied the impact of these mutations in vivo. ... All studied PTHS-associated mutations that we introduced into Da led to similar effects in vivo as the same mutations in TCF4 in vitro. ... our Drosophila models of PTHS are applicable for further studies aiming to unravel the molecular mechanisms of this disorder."