Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly.

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.

authors

Lettice LA,Horikoshi T,Heaney SJ,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

doi

10.1073/pnas.112212199

keywords:

subject

Has Abstract

pub_date

2002-05-28 00:00:00

pages

7548-53

issue

11

eissn

0027-8424

issn

1091-6490

journal_volume

99

pub_type

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