Tenascin-x deficiency mimics ehlers-danlos syndrome in mice through alteration of collagen deposition
- LBNL Library
Tenascin-X is a large extracellular matrix protein of unknown function1-3. Tenascin-X deficiency in humans is associated with Ehlers-Danlos syndrome4,5, a generalized connective tissue disorder resulting from altered metabolism of the fibrillar collagens6. Because TNXB is the first Ehlers-Danlos syndrome gene that does not encode a fibrillar collagen or collagen-modifying enzyme7-14, we suggested that tenascin-X might regulate collagen synthesis or deposition15. To test this hypothesis, we inactivated Tnxb in mice. Tnxb-/- mice showed progressive skin hyperextensibility, similar to individuals with Ehlers-Danlos syndrome. Biomechanical testing confirmed increased deformability and reduced tensile strength of their skin. The skin of Tnxb-/- mice was histologically normal, but its collagen content was significantly reduced. At the ultrastructural level, collagen fibrils of Tnxb-/- mice were of normal size and shape, but the density of fibrils in their skin was reduced, commensurate with the reduction in collagen content. Studies of cultured dermal fibroblasts showed that although synthesis of collagen I by Tnxb-/- and wildtype cells was similar, Tnxb-/- fibroblasts failed to deposit collagen I into cell-associated matrix. This study confirms a causative role for TNXB in human Ehlers-Danlos syndrome and suggests that tenascin-X is an essential regulator of collagen deposition by dermal fibroblasts.
- Research Organization:
- Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (US)
- Sponsoring Organization:
- US Department of Energy (US)
- DOE Contract Number:
- AC03-76SF00098
- OSTI ID:
- 821322
- Report Number(s):
- LBNL--50259
- Journal Information:
- Nature Genetics, Journal Name: Nature Genetics Journal Issue: 4 Vol. 30
- Country of Publication:
- United States
- Language:
- English
Similar Records
Tenascin-X, Collagen, Elastin and the Ehlers-Danlos Syndrome
A large duplication in the gene for lysyl hydroxylase accounts for the type VI variant of Ehlers-Danlos syndrome in two siblings
Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I and II
Journal Article
·
Wed Aug 31 00:00:00 EDT 2005
· Journal of Medical Genetics
·
OSTI ID:889797
A large duplication in the gene for lysyl hydroxylase accounts for the type VI variant of Ehlers-Danlos syndrome in two siblings
Journal Article
·
Sun Jan 31 23:00:00 EST 1993
· Genomics; (United States)
·
OSTI ID:6879912
Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I and II
Journal Article
·
Fri Feb 28 23:00:00 EST 1997
· American Journal of Human Genetics
·
OSTI ID:518538