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Title: Preaxial Polydactyly in Sost/Sostdc1 Double Knockouts

Abstract

In the United States, {approx}5% are born with congenital birth defects due to abnormal function of cellular processes and interactions. Sclerosteosis, a rare autosomal recessive disease, causes hyperostosis of the axial and appendicular skeleton, and patients present radial deviation, digit syndactyly, nail dysplasia, and overall high bone mineral density. Sclerosteosis is due to a loss of function of sclerostin (Sost). Sost is a Wnt (abbrev.) antagonist; when mutated, nonfunctional Sost results in hyperactive osteoblast activity which leads to abnormal high bone mass. Previous studies have shown that Sost overexpression in transgenic mice causes reduced bone mineral density and a variety of limb phenotypes ranging from lost, fused, and split phalanges. Consistent with clinical manifestations of Sclerosteosis, Sost knockout mice exhibit increased generalized bone mineral density and syndactyly of the digits. Sostdc1 is a paralog of Sost that has also been described as an antagonist of Wnt signaling, in developing tooth buds. Unlike Sost knockouts, Sostdc1 null mice do not display any limb abnormalities. To determine if Sost and Sostdc1 have redundant functions during limb patterning, we examined Sost; Sostdc1 mice determined that they exhibit a novel preaxial polydactyly phenotype with a low penetrance. LacZ staining, skeletal preparations, and in situmore » hybridization experiments were used to help characterize this novel phenotype and understand how this phenotype develops. We find Sost and Sostdc1 to have complementary expression patterns during limb development, and the loss of their expression alters the transcription of several key limb regulators, such as Fgf8, Shh and Grem.« less

Authors:
; ;
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1022940
Report Number(s):
LLNL-TR-491664
TRN: US201118%%852
DOE Contract Number:  
W-7405-ENG-48
Resource Type:
Technical Report
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CONNECTIVE TISSUE CELLS; CONGENITAL MALFORMATIONS; DEFECTS; IN-SITU HYBRIDIZATION; MICE; PATIENTS; PHENOTYPE; SKELETON; TRANSCRIPTION; TRANSGENIC MICE

Citation Formats

Yee, C M, Collette, N M, and Loots, G G. Preaxial Polydactyly in Sost/Sostdc1 Double Knockouts. United States: N. p., 2011. Web. doi:10.2172/1022940.
Yee, C M, Collette, N M, & Loots, G G. Preaxial Polydactyly in Sost/Sostdc1 Double Knockouts. United States. doi:10.2172/1022940.
Yee, C M, Collette, N M, and Loots, G G. Fri . "Preaxial Polydactyly in Sost/Sostdc1 Double Knockouts". United States. doi:10.2172/1022940. https://www.osti.gov/servlets/purl/1022940.
@article{osti_1022940,
title = {Preaxial Polydactyly in Sost/Sostdc1 Double Knockouts},
author = {Yee, C M and Collette, N M and Loots, G G},
abstractNote = {In the United States, {approx}5% are born with congenital birth defects due to abnormal function of cellular processes and interactions. Sclerosteosis, a rare autosomal recessive disease, causes hyperostosis of the axial and appendicular skeleton, and patients present radial deviation, digit syndactyly, nail dysplasia, and overall high bone mineral density. Sclerosteosis is due to a loss of function of sclerostin (Sost). Sost is a Wnt (abbrev.) antagonist; when mutated, nonfunctional Sost results in hyperactive osteoblast activity which leads to abnormal high bone mass. Previous studies have shown that Sost overexpression in transgenic mice causes reduced bone mineral density and a variety of limb phenotypes ranging from lost, fused, and split phalanges. Consistent with clinical manifestations of Sclerosteosis, Sost knockout mice exhibit increased generalized bone mineral density and syndactyly of the digits. Sostdc1 is a paralog of Sost that has also been described as an antagonist of Wnt signaling, in developing tooth buds. Unlike Sost knockouts, Sostdc1 null mice do not display any limb abnormalities. To determine if Sost and Sostdc1 have redundant functions during limb patterning, we examined Sost; Sostdc1 mice determined that they exhibit a novel preaxial polydactyly phenotype with a low penetrance. LacZ staining, skeletal preparations, and in situ hybridization experiments were used to help characterize this novel phenotype and understand how this phenotype develops. We find Sost and Sostdc1 to have complementary expression patterns during limb development, and the loss of their expression alters the transcription of several key limb regulators, such as Fgf8, Shh and Grem.},
doi = {10.2172/1022940},
journal = {},
number = ,
volume = ,
place = {United States},
year = {2011},
month = {7}
}

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