Development of the mammalian axial skeleton requires signaling through the Gα(i) subfamily of heterotrimeric G proteins
Autor: | Bernd Nürnberg, Haruhiko Akiyama, Lutz Birnbaumer, Karsten Spicher, Jason Malphurs, Nicholas W. Plummer, Joel Abramowitz |
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Rok vydání: | 2012 |
Předmět: |
musculoskeletal diseases
Sternum Axial skeleton Mice 129 Strain Ribs GNAI1 Biology GTP-Binding Protein alpha Subunits Gi-Go medicine.disease_cause Bone and Bones Mice Myotome Heterotrimeric G protein GNAI3 medicine Animals Alleles Genetics Mammals Mutation Multidisciplinary Bone Development Lumbar Vertebrae Biological Sciences Phenotype Mice Mutant Strains Cell biology Somite medicine.anatomical_structure Spinal Fusion GTP-Binding Protein alpha Subunit Gi2 Signal Transduction |
Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 109(52) |
ISSN: | 1091-6490 |
Popis: | 129/SvEv mice with a loss-of-function mutation in the heterotrimeric G protein α-subunit gene Gnai3 have fusions of ribs and lumbar vertebrae, indicating a requirement for Gα i (the “inhibitory” class of α-subunits) in somite derivatives. Mice with mutations of Gnai1 or Gnai2 have neither defect, but loss of both Gnai3 and one of the other two genes increases the number and severity of rib fusions without affecting the lumbar fusions. No myotome defects are observed in Gnai3 / Gnai1 double-mutant embryos, and crosses with a conditional allele of Gnai2 indicate that Gα i is specifically required in cartilage precursors. Penetrance and expressivity of the rib fusion phenotype is altered in mice with a mixed C57BL/6 × 129/SvEv genetic background. These phenotypes reveal a previously unknown role for G protein-coupled signaling pathways in development of the axial skeleton. |
Databáze: | OpenAIRE |
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