CLONING AND SEQUENCING OF THE MOUSE GLI2 GENE - LOCALIZATION TO THE DOMINANT HEMIMELIA CRITICAL REGION

The GLI family of zinc finger genes has been implicated in both neopla stic and developmental disorders. We have cloned and sequenced the mou se homolog of the zinc finger gene GLi2 and demonstrated significant s imilarity to the human GLI3 gene. We have also localized GLi2 to mouse chromosome 1, in the vicinity of the morphogenetic mutation Dominant hemimelia (Dh), which is characterized by tibial hemimelia, poly/oligo dactyly, and a number of visceral abnormalities, most strikingly absen ce of the spleen. Using a Gli2-associated microsatellite, we demonstra ted no recombination between Dh and GLi2 in a Dh intraspecific backcro ss. GLi2 is expressed in Dh heterozygotes and homozygotes, However, us ing a combination of mismatch analysis and direct sequencing, we have failed to identify any mutations in the coding sequence of GLi2 from D h. We have also demonstrated that it is unlikely that there are any GL i genes in the mouse genome in addition to the previously described GL i, Gli2, and GLi3. (C) 1997 Academic Press