Molecular cloning and expression of the human and mouse homologues of the Drosophila dachshund gene

Recent genetic analysis of the Drosophila dachshund (dac) gene has establis hed that dac encodes;a novel nuclear protein that is involved in both eye a nd leg development. In the Drosophila eye, dac expression appears to be con trolled by the product of the eyeless/Pax6 gene. In order to analyze the Pa x6 pathway in vertebrates we have isolated and characterized the cDNA and g enomic clones corresponding to the human and mouse homologues of Drosophila dac. A full-length human cDNA encoding dachshund (DACH) encodes the 706 am ino acids protein with predicted molecular weight of 73 kDa. A 109 amino ac id domain located at the N-terminus of the DACH showed significant sequence and secondary structure homologies to the ski/sno oncogene products. North ern blot analysis found human DACH predominantly in adult kidney, heart, an d placenta, with less expression detected in the brain, lung, skeletal musc le and pancreas. A panel of human cell lines was studied and most notably a large proportion of neuroblastomas expressed DACH mRNA. Mouse Dach encodes a protein of 751 amino acids with predicted molecular weight of 78 kDa tha t is 95% identical to the human DACH. RNase protection analysis showed the highest Dach mRNA expression in the adult mouse kidney and lung, whereas lo wer expression was detected in the brain and testis. RT/PCR analysis readil y detected Dach mRNA in the adult mouse cornea and retina. Dach mRNA expres sion in the mouse E11.5 embryo was observed primarily in the fore and hind limbs, as well as in the somites.