Functional evaluation of a novel tooth agenesis-associated bone morphogenetic protein 4 prodomain mutation.
Functional evaluation of a novel tooth agenesis-associated bone morphogenetic protein 4 prodomain mutation.
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DOI：
10.1111/eos.12055
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发表时间：
2013-08
影响因子：
1.9
通讯作者：
D'Souza R
中科院分区：
文献类型：
--
作者：
Huang Y;Lu Y;Mues G;Wang S;Bonds J;D'Souza R
The detection of gene mutations in patients with congenitally missing teeth is not very complicated however proving causality is often quite difficult. Here we report the detection of a substitution mutation, A42P, within the prodomain of bone morphogenetic protein-4 (BMP4) in a small family with tooth agenesis and describe a functional alteration that may be responsible for the tooth phenotype. Since BMP4 is essential for the development of teeth but also for many other organs, it would be of considerable interest to find a BMP4 mutation that is only associated with tooth agenesis. Our in vitro investigations revealed that the A42P mutation did neither affect processing and secretion of BMP4 nor alter functional properties like the induction of alkaline phosphatase or signaling through Smad1/5/8 phosphorylation by the mature BMP4 ligand. However immunofluorescent staining revealed that the prodomains of BMP4 which harbor the A42P substitution, form fibrillar structures around transfected cells in culture and that this fibrillar network is significantly decreased when mutant prodomains are expressed. Our finding suggests that in vivo, BMP4 prodomain behavior might also be altered by the mutation and could influence storage or transport of mature BMP4 in the extracellular matrix of the developing tooth.
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影响因子：
2
作者：
Mues, Gabriele I.;Griggs, Rachel;D'Souza, Rena
通讯作者：
D'Souza, Rena
影响因子：
4.8
作者：
Nelsen, Sylvia M.;Christian, Jan L.
通讯作者：
Christian, Jan L.
影响因子：
64.5
作者：
VAINIO, S;KARAVANOVA, I;THESLEFF, I
通讯作者：
THESLEFF, I
影响因子：
4
作者：
van den Boogaard, Marie-Jose;Creton, Marijn;van Amstel, Hans Kristian Ploos
通讯作者：
van Amstel, Hans Kristian Ploos
影响因子：
9.8
作者：
Lammi, L;Arte, S;Nieminen, P
通讯作者：
Nieminen, P