Disruption of a Long-range Cis-acting Regulator for Shh Causes Preaxial Polydactyly

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2002 May 29

PMID 12032320

Citations 187

Authors

Laura A Lettice

Taizo Horikoshi

Simon J H Heaney

Marijke J van Baren

Herma C van der Linde

Guido J Breedveld

Marijke Joosse

Nurten Akarsu

Ben A Oostra

Naoto Endo

Minoru Shibata

Mikio Suzuki

Eiichi Takahashi

Toshikatsu Shinka

Yutaka Nakahori

Dai Ayusawa

Kazuhiko Nakabayashi

Stephen W Scherer

Peter Heutink

Robert E Hill

Sumihare Noji

Affiliations

Soon will be listed here.

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.

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