Disruption Of A Long-Range Cis-Acting Regulator For Shh Causes Preaxial Polydactyly
- Lettice, LA
- Horikoshi, T
- Heaney, SJH
- van Baren, MJ
- van der Linde, HC
- Breedveld, GJ
- Joosse, M
- Akarsu, N
- Oostra, BA
- Endo, N
- Shibata, M
- Suzuki, M
- Takahashi, E
- Shinka, T
- Nakahori, Y
- Ayusawa, D
- Nakabayashi, K
- Scherer, SW
- Heutink, P
- Hill, RE
- Noji, S
Publication date
January 2002
DOI Publisher
Proceedings of the National Academy of Sciences Journal
Proceedings of the National Academy of SciencesAbstract
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 approximate to1 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.Wo
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