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Esophageal muscle physiology and morphogenesis require assembly of a collagen XIX-rich basement membrane zone.

Collagen XIX is an extremely rare extracellular matrix component that localizes to basement membrane zones and is transiently expressed by differentiating muscle cells. Characterization of mice harboring null and structural mutations of the collagen XIX (Col19a1) gene has revealed the critical contribution of this matrix protein to muscle physiology and differentiation. The phenotype includes smooth muscle motor dysfunction and hypertensive sphincter resulting from impaired swallowing-induced, nitric oxide-dependent relaxation of the sphincteric muscle. Muscle dysfunction was correlated with a disorganized matrix and a normal complement of enteric neurons and interstitial cells of Cajal. Mice without collagen XIX exhibit an additional defect, namely impaired smooth-to-skeletal muscle cell conversion in the abdominal segment of the esophagus. This developmental abnormality was accounted for by failed activation of myogenic regulatory factors that normally drive esophageal muscle transdifferentiation. Therefore, these findings identify collagen XIX as the first structural determinant of sphincteric muscle function, and as the first extrinsic factor of skeletal myogenesis in the murine esophagus.

Pubmed ID: 15302855 RIS Download

Mesh terms: Animals | Basement Membrane | Cell Differentiation | Coiled Bodies | Collagen | Esophagogastric Junction | Esophagus | Extracellular Matrix | Mice | Muscles | Mutation | Neurons | Nitric Oxide | Phenotype

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Associated grants

  • Agency: NIAMS NIH HHS, Id: R01 AR038648
  • Agency: NIDDK NIH HHS, Id: DK-35385
  • Agency: NIDDK NIH HHS, Id: R01 DK035385
  • Agency: NIAMS NIH HHS, Id: AR-38648
  • Agency: NIAMS NIH HHS, Id: R37 AR038648
  • Agency: NCI NIH HHS, Id: R24 CA095823
  • Agency: NCI NIH HHS, Id: CA-095823

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