Tenascin-X, Collagen, Elastin and the Ehlers-Danlos Syndrome

Journal Article · Wed Aug 31 04:00:00 EDT 2005 · Journal of Medical Genetics

DOI:https://doi.org/10.1002/ajmg.c.30071· OSTI ID:889797

Bristow, James; Carey, William; Schalkwijk, Joost

Tenascin-X is an extracellular matrix protein initially identified because of its overlap with the human CYP21B gene. Because studies of gene and protein function of other tenascins had been poorly predictive of essential functions in vivo, we used a genetic approach that critically relied on an understanding of the genomic locus to uncover an association between inactivating tenascin-X mutations and novel recessive and dominant forms of Ehlers-Danlos syndrome. Tenascin-X provides the first example of a gene outside of the fibrillar collagens and their processing enzymes that causes Ehlers-Danlos syndrome. Tenascin-X null mice recapitulate the skin findings of the human disease, confirming a causative role for this gene in Ehlers-Danlos syndrome. Further evaluation of these mice showed that tenascin-X is an important regulator of collagen deposition in vivo, suggesting a novel mechanism of disease in this form of Ehlers-Danlos syndrome. Further studies suggest that tenascin-X may do this through both direct and indirect interactions with the collagen fibril. Recent studies show that TNX effects on matrix extend beyond the collagen to the elastogenic pathway and matrix remodeling enzymes. Tenascin-X serves as a compelling example of how human experiments of nature can guide us to an understanding of genes whose function may not be evident from their sequence or in vitro studies of their encoded proteins.

• Research Organization: Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
• Sponsoring Organization: USDOE Director, Office of Science; National Institutes ofHealth
• DOE Contract Number: AC02-05CH11231
• OSTI ID: 889797
• Report Number(s): LBNL--58738; BnR: 400412000
• Journal Information: Journal of Medical Genetics, Journal Name: Journal of Medical Genetics Journal Issue: 1 Vol. 139; ISSN 0022-2593; ISSN JMDGAE
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
COLLAGEN
DEPOSITION
DISEASES
ENZYMES
EVALUATION
GENES
GENETICS
IN VITRO
IN VIVO
MICE
MUTATIONS
PROCESSING
PROTEINS