Mouse model of split hand/foot malformation type I.

Giorgio R Merlo (1) , Laura Paleari (2) , Stefano Mantero (2) , Francesca Genova (2) , Annemiek Beverdam (2) , Giulio L Palmisano (2) , Ottavia Barbieri (2) , Giovanni Levi (2, 3)

1 Dulbecco Telethon Institute
2 Istituto Nazionale per la Ricerca sul Cancro, Genoa
3 ERE - Evolution des régulations endocriniennes

Split hand/foot malformation type I (SHFM1) disease locus maps to chromosome 7q21.3-q22, a region that includes the distal-less-related (dll) genes DLX5 and DLX6. However, incomplete penetrance, variable expressivity, segregation distortion, and syndromic association with other anomalies have so far prevented the identification of the SHFM1 gene(s) in man. Here we show that the targeted double inactivation of Dlx5 and Dlx6 in the mouse causes in homozygous mutant animals bilateral ectrodactyly with a severe defect of the central ray of the hindlimbs, a malformation typical of SHFM1. This is the first evidence that the role of dll/Dlx genes in appendage development is conserved from insects to mammals and proves their involvement in SHFM1.

Domaines: Biologie du développement

Giorgio R Merlo, Laura Paleari, Stefano Mantero, Francesca Genova, Annemiek Beverdam, et al.. Mouse model of split hand/foot malformation type I.. Genesis, 2002, 33 (2), pp.97-101. ⟨10.1002/gene.10098⟩. ⟨hal-00181136⟩