دورية أكاديمية
Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg anophthalmia) syndrome in humans and mice
| العنوان: | Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg anophthalmia) syndrome in humans and mice |
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| المؤلفون: | van Beusekom, E., Rainger, J., Ramsay, J.K., McKie, L., Al-Gazali, L., Pallotta, R., Saponari, A. |
| بيانات النشر: | Public Library of Science |
| سنة النشر: | 2011 |
| المجموعة: | Pamukkale University Repository / Pamukkale Üniversitesi Açık Erişim Arşivi |
| مصطلحات موضوعية: | decapentaplegic protein, Drosophila, embryo, female, frameshift mutation, loss of function mutation, male, microsatellite marker, missense mutation, mouse, mutational analysis, bone morphogenetic protein, messenger RNA, BMP1 protein, human, osteonectin, procollagen C proteinase, SMOC 1 protein, SMOC-1 protein, SMOC1 protein, adolescent, adult, animal tissue, article, child, cleft palate, clinical article, coloboma, down regulation, gene |
| الوصف: | Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1tm1a) that reduces mRNA to ~10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1tm1a/tm1a). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1tm1a/tm1a embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice. © 2011 Rainger et al. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1553-7390 |
| العلاقة: | PLoS Genetics; Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı; https://doi.org/10.1371/journal.pgen.1002114Test; https://hdl.handle.net/11499/6179Test; 2-s2.0-79960938476; WOS:000293338600004 |
| DOI: | 10.1371/journal.pgen.1002114 |
| الإتاحة: | https://doi.org/10.1371/journal.pgen.1002114Test https://hdl.handle.net/11499/6179Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.C1BDA33E |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15537390 |
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| DOI: | 10.1371/journal.pgen.1002114 |