Disruption of a long-range cis-acting regulator for <i>Shh</i> causes preaxial polydactyly
Laura A. Lettice(Niigata University), Taizo Horikoshi(Niigata University), Simon J. H. Heaney(Niigata University), Marijke J. van Baren(Niigata University), Herma C. van der Linde(Niigata University), Guido J. Breedveld(Niigata University), Marijke Joosse(Niigata University), Nurten Akarsu(Niigata University), Ben A. Oostra(Niigata University), Naoto Endo(Niigata University), Minoru Shibata(Niigata University), Mikio Suzuki(Niigata University), Eiichi Takahashi(Niigata University), Toshikatsu Shinka(Niigata University), Yutaka Nakahori(Niigata University), Dai Ayusawa(Niigata University), Kazuhiko Nakabayashi(Niigata University), Stephen W. Scherer(Niigata University), Peter Heutink(Niigata University), Robert E. Hill(Niigata University), Sumihare Noji(Niigata University)
Cited by 456Open Access
Abstract
Preaxial polydactyly (PPD) is a common limb malformation in human. A number of polydactylous mouse mutants indicate that misexpression of Shh is a common requirement for generating extra digits. Here we identify a translocation breakpoint in a PPD patient and a transgenic insertion site in the polydactylous mouse mutant sasquatch (Ssq). The genetic lesions in both lie within the same respective intron of the LMBR1/Lmbr1 gene, which resides approximately 1 Mb away from Shh. Genetic analysis of Ssq reveals that the Lmbr1 gene is incidental to the phenotype and that the mutation directly interrupts a cis-acting regulator of Shh. This regulator is most likely the target for generating PPD mutations in human.