Due to necessary maintenance, Xenbase will be unavailable December 24-30, 2014. We apologize for the inconvenience.

Click on this message to dismiss it.
Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-8378
Proc Natl Acad Sci U S A. September 25, 2001; 98 (20): 11353-8.

Human disease-causing NOG missense mutations: effects on noggin secretion, dimer formation, and bone morphogenetic protein binding.

Marcelino J , Sciortino CM , Romero MF , Ulatowski LM , Ballock RT , Economides AN , Eimon PM , Harland RM , Warman ML .


Abstract
Secreted noggin protein regulates bone morphogenetic protein activity during development. In mice, a complete loss of noggin protein leads to multiple malformations including joint fusion, whereas mice heterozygous for Nog loss-of-function mutations are normal. In humans, heterozygous NOG missense mutations have been found in patients with two autosomal dominant disorders of joint development, multiple synostosis syndrome (SYNS1) and a milder disorder proximal symphalangism (SYM1). This study investigated the effect of one SYNS1 and two SYM1 disease-causing missense mutations on the structure and function of noggin. The SYNS1 mutation abolished, and the SYM1 mutations reduced, the secretion of functional noggin dimers in transiently transfected COS-7 cells. Coexpression of mutant noggin with wild-type noggin, to resemble the heterozygous state, did not interfere with wild-type noggin secretion. These data indicate that the human disease-causing mutations are hypomorphic alleles that reduce secretion of functional dimeric noggin. Therefore, we conclude that noggin has both species-specific and joint-specific dosage-dependent roles during joint formation. Surprisingly, in contrast to the COS-7 cell studies, the SYNS1 mutant was able to form dimers in Xenopus laevis oocytes. This finding indicates that there also exist species-specific differences in the ability to process mutant noggin polypeptides.

PubMed ID: 11562478
PMC ID: PMC58733
Article link: Proc Natl Acad Sci U S A.
Grant support: AR 43527 NIAMS NIH HHS , GM 49346 NIGMS NIH HHS , HD 07014 NICHD NIH HHS

Genes referenced: mpv17 nog
Antibodies referenced:
Morpholinos referenced:
Article Images: [+] show captions

My Xenbase: [ Log-in / Register ]
version: [3.3.1]


Major funding for Xenbase is provided by the National Institute of Child Health and Human Development, grant P41 HD064556