Tenascin-X deficiency mimics Ehlers-Danlos syndrome in mice through alteration of collagen deposition
Abstract
Tenascin-X is a large extracellular matrix protein of unknown function. Tenascin-X deficiency in humans is associated with Ehlers-Danlos syndrome, a generalized connective tissue disorder resulting from altered metabolism of the fibrillar collagens. Because TNXB is the first Ehlers-Danlos syndrome gene that does not encode a fibrillar collagen or collagen-modifying enzyme, we suggested that tenascin-X might regulate collagen synthesis or deposition. 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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
TNXB encodes tenascin-X, which is highly expressed in connective tissues; it is essential in the maintenance of the integrity of the extracellular matrix by regulating collagen fibril deposition, in which defects lead to EDS.
“TNXB encodes tenascin-X, which is highly expressed in connective tissues. It is essential in the maintenance of the integrity of the extracellular matrix by regulating the collagen fi bril deposition, in which defects lead to EDS, a hereditary connective tissue disorder. 21”
From High-Throughput Screening for CYP21A1P-TNXA/TNXB Chimeric Genes Responsible for Ehlers Danlos Syndrome in Patients with Congenital Adrenal Hyperplasia. (2019) · cites this paper as [21]
Cites
A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency
Schalkwijk, J., Zweers, M. C., Steijlen, P. M., Dean, W. B., Taylor, G., van Vlijmen, I. M., van Haren, B., Miller, W. L., & Bristow, J. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa002939 · Cited by 391 · see citing works
Self-citationTenascin-X deficiency is associated with Ehlers-Danlos syndrome
Burch, G. H., Gong, Y., Liu, W., Dettman, R. W., Curry, C. J., Smith, L., Miller, W. L., & Bristow, J. (1997) · Nature Genetics · doi:10.1038/ng0997-104 · Cited by 366 · see citing works
Self-citationTumour invasion and metastasis are promoted in mice deficient in tenascin‐X
Matsumoto, K., Takayama, N., Ohnishi, J., Ohnishi, E., Shirayoshi, Y., Nakatsuji, N., & Ariga, H. (2001) · Genes to Cells · doi:10.1046/j.1365-2443.2001.00482.x · Cited by 81 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Matricellular proteins: extracellular modulators of cell function
BORNSTEIN, P. K., & Sage, E. H. (2002) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(02)00361-7 · Cited by 966 · see citing works
The myofibroblast matrix: implications for tissue repair and fibrosis
Klingberg, F., Hinz, B., & White, E. S. (2013) · The Journal of Pathology · doi:10.1002/path.4104 · Cited by 776 · see citing works
“skin [158,159].”
Collagen fibrillogenesis: fibronectin, integrins, and minor collagens as organizers and nucleators
Kadler, K. E., Hill, A., & Canty‐Laird, E. G. (2008) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2008.06.008 · Cited by 757 · see citing works
Type V collagen controls the initiation of collagen fibril assembly
Wenstrup, R. J., Florer, J. B., Brunskill, E. W., Bell, S. M., Chervoneva, I., & Birk, D. E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409622200 · Cited by 545 · see citing works
Tenascins: regulation and putative functions during pathological stress
Chiquet-Ehrismann, R., & Chiquet, M. (2003) · Journal of Pathology · doi:10.1002/path.1415 · Cited by 557 · see citing works
“Furthermore, a tenascinX-deficient mouse model was created that exhibited similar phenotypes to the human disease [24].”
BackgroundMatricellular Proteins in Cardiac Adaptation and Disease
Frangogiannis, N. G. (2012) · Physiological Reviews · doi:10.1152/physrev.00008.2011 · Cited by 440 · see citing works
“However, tenascin-X absence did not result in any gross cardiac abnormalities (279).”
BackgroundCongenital adrenal hyperplasia due to 21-hydroxylase deficiency
Merke, D. P., & Auchus, R. J. (2020) · New England Journal of Medicine · doi:10.1056/nejmra1909786 · Cited by 341 · see citing works
Velling, T., Risteli, J., Wennerberg, K., Mosher, D., & Johansson, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206286200 · Cited by 339 · see citing works
Regulation of angiogenesis by extracellular matrix
Sottile, J. (2003) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2003.07.002 · Cited by 291 · see citing works
Genomic Organization of the Mammalian Mhc
Kumánovics, A., Takada, T., & Lindahl, K. F. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.090501.080116 · Cited by 247 · see citing works
Tenascins and the Importance of Adhesion ModulationPreprint
Chiquet‐Ehrismann, R., & Tucker, R. P. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a004960 · Cited by 272 · see citing works
“Abnormal epidermal scars, hyperextensible skin, fragile skin, reduced dermal fibrillar collagen, abnormal fibrillar collagen Mao et al. 2002; Minamitani et al. 2004a, 2004b; Egging et al. 2006, 2007 Miscellaneous phenotypes Abnormal vaginal plug location, rectal prolapse Egging et al. 2008 Abnormal…”
BackgroundBradshaw, A., Puolakkainen, P., Dasgupta, J., Davidson, J., Wight, T., & Sage, E. (2003) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2003.12241.x · Cited by 245 · see citing works
Haploinsufficiency of TNXB Is Associated with Hypermobility Type of Ehlers-Danlos Syndrome
Zweers, M. C., Bristow, J., Steijlen, P. M., Dean, W. B., Hamel, B. C., Otero, M., Kucharekova, M., Boezeman, J. B., & Schalkwijk, J. (2003) · The American Journal of Human Genetics · doi:10.1086/376564 · Cited by 242 · see citing works
Self-citationJepsen, K., Wu, F., Peragallo, J., Paul, J., Roberts, L., Ezura, Y., Oldberg, Å., Birk, D., & Chakravarti, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205398200 · Cited by 237 · see citing works
Vascular extracellular matrix and aortic development.
Kelleher, C. M., Mclean, S., & Mecham, R. (2004) · Current Topics in Developmental Biology · doi:10.1016/s0070-2153(04)62006-0 · Cited by 222 · see citing works
“No vascular defects or diseases have been linked to mutations within any of the tenascin genes, nor do knockout animals display a vascular phenotype (Mackie and Tucker, 1999; Mao et al., 2002).”
BackgroundCell-matrix interactions in dermal repair and scarring
Eckes, B., Nischt, R., & Krieg, T. (2010) · Fibrogenesis & Tissue Repair · doi:10.1186/1755-1536-3-4 · Cited by 205 · see citing works
“Although patient skin is characterized by reduced density of collagen fibers and abnormal elastin fibers [38], scars are not atrophic but tend to be wider than normal, and scar tissue in tenascin-X null mice has reduced stability [39].”
BackgroundMatricellular proteins in the heart: possible role during stress and remodeling.
Schellings, M., Pinto, Y., & Heymans, S. (2004) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.06.006 · Cited by 202 · see citing works
“These gene deficient mice only show a mild phenotype after birth, mainly consisting of some abnormalities of collagen formation, with resulting hyperflexibility of the skin as described in TN-X and TSP2 deficient mice [3,4].”
BackgroundInfluentialNavigating ECM barriers at the invasive front: the cancer cell-stroma interface.
Rowe, R., & Weiss, S. J. (2009) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.24.110707.175315 · Cited by 201 · see citing works
What Mouse Mutants Teach Us About Extracellular Matrix Function
Aszódi, A., Legate, K. R., Nakchbandi, I. A., & Fässler, R. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.22.010305.104258 · Cited by 184 · see citing works
“Tenascin-X deficiency causes reduced collagen I content in the skin, leading to skin hyperextensibility and mimicking the mutation in the human TNXB gene that causes EhlersDanlos syndrome (Mao et al. 2002).”
BackgroundFibronectin-dependent collagen I deposition modulates the cell response to fibronectin
Sottile, J., Shi, F., Rublyevska, I., Chiang, H., Lust, J., & Chandler, J. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00130.2007 · Cited by 187 · see citing works
“Mice lacking tenascin X have reduced collagen I content and lower density of type I collagen fibrils in skin, despite normal collagen synthesis (51).”
BackgroundNakayama, R., Nemoto, T., Takahashi, H., Ohta, T., Kawai, A., Seki, K., Yoshida, T., Toyama, Y., Ichikawa, H., & Hasegawa, T. (2007) · Modern Pathology · doi:10.1038/modpathol.3800794 · Cited by 175 · see citing works
Sun, M., Chen, S., Adams, S. M., Florer, J. B., Liu, H., Kao, W. W. ‐., WENSTRUP, R. J., & Birk, D. E. (2011) · Journal of Cell Science · doi:10.1242/jcs.091363 · Cited by 193 · see citing works
“For instance, mutations in tenascin X lead to an EDS phenotype in the presence of normal collagen V (Bristow et al., 2005; Mao et al., 2002).”
BackgroundLysyl Oxidase Activity Is Required for Ordered Collagen Fibrillogenesis by Tendon Cells*
Herchenhan, A., Uhlenbrock, F., Eliasson, P., Weis, M., Eyre, D., Kadler, K., Magnusson, S., & Kjaer, M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.641670 · Cited by 168 · see citing works
Meet the Tenascins: Multifunctional and Mysterious
Hsia, H. C., & Schwarzbauer, J. E. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.r500005200 · Cited by 176 · see citing works
Connective tissues: signalling by tenascins.
Chiquet-Ehrismann, R., & Tucker, R. (2004) · International Journal of Biochemistry and Cell Biology · doi:10.1016/j.biocel.2004.01.007 · Cited by 164 · see citing works
“Mice deficient in tenascin-X have a hyperstretchable skin accompanied by reduced amounts of collagen fibers (Mao et al., 2002).”
BackgroundSPARC Regulates Processing of Procollagen I and Collagen Fibrillogenesis in Dermal Fibroblasts
Rentz, T. J., Poobalarahi, F., BORNSTEIN, P. K., Sage, E. H., & Bradshaw, A. D. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700167200 · Cited by 160 · see citing works
Matricellular proteins as modulators of wound healing and the foreign body response
Kyriakides, T., & Bornstein, P. (2003) · Thrombosis and Haemostasis · doi:10.1160/th03-06-0399 · Cited by 151 · see citing works
“Tenascin-X-null mice manifest a phenotype that resembles a form of Ehlers-Danlos syndrome (53), and is similar to that of TSP2-null mice in some respects.”
BackgroundGensemer, C., Burks, R., Kautz, S. A., Judge, D. P., Lavallee, M. E., & Norris, R. A. (2020) · Developmental Dynamics · doi:10.1002/dvdy.220 · Cited by 151 · see citing works
“Despite TNXB not encoding for collagen or any enzyme involved in collagen modification, it was revealed to play a role in collagen deposition though studies involving inactivation of Tenascin-X in a murine model of EDS.(240) Tenascin-X knockout mice also exhibit mild muscular features and evidence of increased ECM tur…”
BackgroundImmunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment
McQuitty, C. E., Williams, R., Chokshi, S., & Urbani, L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.574276 · Cited by 146 · see citing works
WENSTRUP, R. J., Smith, S. M.-L., Florer, J. B., Zhang, G., Beason, D. P., Seegmiller, R. E., Soslowsky, L. J., & Birk, D. E. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.223693 · Cited by 161 · see citing works
Collagen Fibril Assembly and Function.
Holmes, D. F., Lu, Y.-H., Starborg, T., & Kadler, K. (2018) · Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2018.02.004 · Cited by 145 · see citing works
Malfait, F., Kariminejad, A., Van Damme, T., Gauche, C., Syx, D., Merhi-Soussi, F., Gulberti, S., Symoens, S., Vanhauwaert, S., Willaert, A., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.04.016 · Cited by 142 · see citing works
Disorders of Connective Tissue
Burrows, N., & Lovell, C. R. (2004) · Wiley eBooks · doi:10.1002/9780470750520.ch46 · Cited by 91 · see citing works
Whole genome association study of rheumatoid arthritis using 27 039 microsatellites
Tamiya, G., Shinya, M., Imanishi, T., Ikuta, T., Makino, S., Okamoto, K., Furugaki, K., Matsumoto, T., Mano, S., Ando, S., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi234 · Cited by 129 · see citing works
“It is involved in a yet unknown manner in collagen fibril deposition in connective tissues (32).”
Tenascin-X: beyond the architectural function
Valcourt, U., Alcaraz, L. B., Exposito, J.-Y., Lethias, C., & Bartholin, L. (2015) · Cell Adhesion & Migration · doi:10.4161/19336918.2014.994893 · Cited by 132 · see citing works
“Interestingly, the genetic background markedly influences EDS manifestations, as the phenotype was less severe on a homogenous (C57BL/6) compared to a mixed (129/SvJ, C57BL/6 and FVB) genetic background.(29,47,49) One possible Figure 2.”
BackgroundResultInfluentialModulation of collagen fibrillogenesis by tenascin-X and type VI collagen
Minamitani, T., Ikuta, T., Saito, Y., Takebe, G., Sato, M., Sawa, H., Nishimura, T., Nakamura, F., Takahashi, K., Ariga, H., et al. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.04.030 · Cited by 126 · see citing works
Zhou, C., Hui, Miao, K., Bahr, T. A., Qiong, Zhang, Y., Liang, T., Huai, Zhou, B., Guo, et al. (2020) · Molecular Carcinogenesis · doi:10.1002/mc.23198 · Cited by 124
“It is well known that TNXB deficiency is associated with Ehlers‐Danlos syndrome, a connective tissue disorder resulting from altered fibrillar collagens metabolism.(21,22) However, the role of TNXB in tumorigenesis has not been well characterized.”
Overlapping genes in vertebrate genomes
Makałowska, I., Lin, C.-F., & Makałowski, W. (2005) · Comput. Biol. Chem. · doi:10.1016/j.compbiolchem.2004.12.006 · Cited by 121 · see citing works
Desai, J. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl053 · Cited by 110 · see citing works
“EDS patients do not have the ability to make certain components of the connective tissue, particularly fibrillar collagens, or they have defective regulation of collagen synthesis and deposition (22,23).”
BackgroundKoester, J., Miroshnikova, Y. A., Ghatak, S., Chacón-Martínez, C. A., Morgner, J., Li, X., Atanassov, I., Altmüller, J., Birk, D. E., Koch, M., et al. (2021) · Nature Cell Biology · doi:10.1038/s41556-021-00705-x · Cited by 117 · see citing works
Tenascin‐X, collagen, elastin, and the Ehlers–Danlos syndrome
Bristow, J. D., Carey, W. A., Egging, D. F., & Schalkwijk, J. (2005) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.30071 · Cited by 122 · see citing works
“Tnx null mice are”
BackgroundInfluentialSelf-citationCollagens, Suprastructures, and Collagen Fibril Assembly
Birk, D. E., & Brückner, P. (2010) · Springer eBooks · doi:10.1007/978-3-642-16555-9_3 · Cited by 114 · see citing works
Collagen fibril assembly: New approaches to unanswered questions
Revell, C. K., Jensen, O. E., Tom Shearer, N., Lu, Y., Holmes, D. F., & Kadler, K. E. (2021) · Matrix Biology Plus · doi:10.1016/j.mbplus.2021.100079 · Cited by 122 · see citing works
A unified multiscale mechanical model for soft collagenous tissues with regular fiber arrangement.
Maceri, F., Marino, M., & Vairo, G. (2010) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2009.07.040 · Cited by 108 · see citing works
“For instance, some clinical disorders (such as Ehlers–Danlos syndrome) are associated to the reduction of collagen content (up to 50%, Mao et al., 2002), leading to joint hypermobility or higher risk of vascular rupture (Mao and Bristow, 2001).”
BackgroundGoldsmith, E. C., Bradshaw, A. D., & Spinale, F. G. (2012) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00347.2012 · Cited by 101 · see citing works
“Tenascin C None reported No differences detected (60) MI: decreased collagen content in border zone (60) Tenascin X Reduced dermal fibril density (53) Not characterized Not characterized”
BackgroundCollagen XII Interacts with Avian Tenascin-X through Its NC3 Domain*
Veit, G., Hansen, U., Keene, D., Bruckner, P., Chiquet-Ehrismann, R., Chiquet, M., & Koch, M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603147200 · Cited by 104 · see citing works
Wilson, R., Norris, E. L., Brachvogel, B., Angelucci, C., Živković, S., Gordon, L., Bernardo, B., Stermann, J., Sekiguchi, K., Gorman, J., et al. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.014159 · Cited by 103 · see citing works
Severe Osteogenesis Imperfecta in Cyclophilin B–Deficient Mice
Choi, J.-W., Sutor, S., Lindquist, L. D., Evans, G. L., Madden, B., Bergen, H. R., Hefferan, T., Yaszemski, M., & Bram, R. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000750 · Cited by 103 · see citing works
“Skin from 38-weeks old female mice was biomechanically tested for tensile strength as described [23].”
BackgroundMethodInfluentialMolecular genetics in classic Ehlers–Danlos syndrome
Malfait, F., & Paepe, A. D. (2005) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.30070 · Cited by 109 · see citing works
“Tenascin-X is a large extracellular matrix protein of which the function is not yet completely understood, but that is thought to play an important role in the regulation of collagen deposition by dermal fibroblasts [Mao et al., 2002].”
BackgroundTranscriptional regulation of tenascin genes
Chiovaro, F., Chiquet‐Ehrismann, R., & Chiquet, M. (2015) · Cell Adhesion & Migration · doi:10.1080/19336918.2015.1008333 · Cited by 120 · see citing works
“126 Thus, in apparent contrast to the other tenascins, TNX protein has a clear structural role in connective tissue integrity.”
Proteomics Characterization of Extracellular Space Components in the Human Aorta
Didangelos, A., Yin, X.-K., Mandal, K., Baumert, M., Jahangiri, M., & Mayr, M. (2010) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m110.001693 · Cited by 99 · see citing works
Tenascin-X promotes epithelial-to-mesenchymal transition by activating latent TGF-β
Alcaraz, L. B., Exposito, J.-Y., Chuvin, N., Pommier, R. M., Cluzel, C., Martel, S., Sentis, S., Bartholin, L., Lethias, C., & Valcourt, U. (2014) · Journal of Cell Biology · doi:10.1083/jcb.201308031 · Cited by 94 · see citing works
“Moreover, deficiency or haploinsufficiency of TNX both in patients and mice is correlated with a decreased content of collagen and elastic fibers in connective tissues, thus compromising their biomechanical properties (Mao et al., 2002; Zweers et al., 2004).”
Cipriani, V., Leung, H.-T., Plagnol, V., Bunce, C., Khan, J. C., Shahid, H., Moore, A. T., Harding, S. P., Bishop, P. N., Hayward, C., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds225 · Cited by 89 · see citing works
Congenital adrenal hyperplasia
Auer, M. K., Nordenström, A., Lajić, S., & Reisch, N. (2022) · The Lancet · doi:10.1016/s0140-6736(22)01330-7 · Cited by 232 · see citing works
Deficiency of tenascin-X causes abnormalities in dermal elastic fiber morphology.
Zweers, M., van Vlijmen-Willems, I., van Kuppevelt, T., Mecham, R., Steijlen, P., Bristow, J., & Schalkwijk, J. (2004) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2004.22401.x · Cited by 91 · see citing works
Self-citationScherberich, A., Tucker, R. P., Samandari, E., Brown-Luedi, M., Martin, D., & Chiquet-Ehrismann, R. (2004) · Journal of Cell Science · doi:10.1242/jcs.00867 · Cited by 90 · see citing works
“Tenascin-X knockout mice also develop outwardly normally but eventually display connective tissue disorders resembling Ehlers-Danlos syndrome (Mao et al., 2002).”
Mosher, D., & Adams, J. C. (2012) · Matrix Biology · doi:10.1016/j.matbio.2012.01.003 · Cited by 89 · see citing works
Joint hypermobility syndromes: The pathophysiologic role of tenascin‐X gene defects
Zweers, M. C., Hakim, A. J., Grahame, R., & Schalkwijk, J. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20488 · Cited by 91 · see citing works
Chang, J., Zhong, R., Tian, J., Li, J., Zhai, K., Ke, J., Lou, J., Chen, W., Zhu, B., Shen, N., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0045-8 · Cited by 90 · see citing works
Tenascin-X Mediates Flow-Induced Suppression of EndMT and Atherosclerosis
Liang, G., Wang, S., Shao, J., Jin, Y., Xu, L., Yang, Y., Günther, S., Wang, L., & Offermanns, S. (2022) · Circulation Research · doi:10.1161/circresaha.121.320694 · Cited by 104 · see citing works
Merke, D. P., Chen, W., Morissette, R., Xu, Z., Van Ryzin, C., Sachdev, V., Hannoush, H., Shanbhag, S. M., Acevedo, A. T., Nishitani, M., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3148 · Cited by 82 · see citing works
Juneja, S., & Veillette, C. (2013) · Arthritis · doi:10.1155/2013/154812 · Cited by 82
Ishikawa, Y., Vranka, J. A., Boudko, S. P., Pokidysheva, E. N., Mizuno, K., Zientek, K. D., Keene, D. R., Rashmir‐Raven, A. M., Nagata, K., Winand, N. J., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.333336 · Cited by 79 · see citing works
Egbert, M., Ruetze, M., Sattler, M., Wenck, H., Gallinat, S., Lucius, R., & Weise, J. M. (2014) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2013.08.010 · Cited by 77 · see citing works
“These include thrombospondins [31,32], SPARC [33], hevin [34], tenascin-X [35], CCN1 [36,37], CCN2 [38,39], and”
BackgroundRole of matricellular proteins in cardiac tissue remodeling after myocardial infarction
Matsui, Y. (2010) · World Journal of Biological Chemistry · doi:10.4331/wjbc.v1.i5.69 · Cited by 73 · see citing works
First Mouse Model for Combined Osteogenesis Imperfecta and Ehlers‐Danlos Syndrome
Chen, F., Guo, R.-L., Itoh, S., Moreno, L., Rosenthal, E., Zappitelli, T., Zirngibl, R., Flenniken, A., Cole, W., Grynpas, M., et al. (2014) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2177 · Cited by 76 · see citing works
Gene expression profiles from hypertrophic scar fibroblasts before and after IL‐6 stimulation
Dasu, M., Hawkins, H. K., Barrow, R. E., Xue, H.-S., & Herndon, D. (2004) · Journal of Pathology · doi:10.1002/path.1539 · Cited by 76 · see citing works
“Tenascin X associates with heterotypic collagen fibrils and facilitates fibril deposition both in vivo and in vitro [45].”
BackgroundA model of tenascin-X integration within the collagenous network
Lethias, C., Carisey, A., Comte, J., Cluzel, C., & Exposito, J.-Y. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.10.037 · Cited by 74 · see citing works
Early aldosterone-regulated genes in cardiomyocytes: clues to cardiac remodeling?
Fejes-Tóth, G., & Náray-Fejes-Tóth, A. (2007) · Endocrinology · doi:10.1210/en.2006-1438 · Cited by 74 · see citing works
Bader, H., Keene, D., Charvet, B., Veit, G., Driever, W., Koch, M., & Ruggiero, F. (2009) · Matrix Biology · doi:10.1016/j.matbio.2008.09.580 · Cited by 72 · see citing works
Wenstrup, R., Florer, J., Cole, W., Willing, M., & Birk, D. (2004) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20024 · Cited by 71 · see citing works
“A reduction of type I collagen deposition was also observed in cultured dermal fibroblasts from tenascin X (TNX) deficientmice, which hadnormal type I collagen synthesis but reduced collagen deposition in cell culture [Mao et al., 2002].”
BackgroundMatricellular proteins in the trabecular meshwork.
Rhee, D., Haddadin, R. I., Kang, M., & Oh, D.-J. (2009) · Experimental Eye Research · doi:10.1016/j.exer.2008.11.032 · Cited by 70 · see citing works
Interactions of human tenascin-X domains with dermal extracellular matrix molecules
Egging, D. F., van den Berkmortel, F., Taylor, G. D., Bristow, J., & Schalkwijk, J. (2006) · Archives of Dermatological Research · doi:10.1007/s00403-006-0706-9 · Cited by 66 · see citing works
“In mice, the variation in collagen Wbril diameter appears to be increased [ 15 , 18].”
BackgroundSelf-citationBroadening the Spectrum of Ehlers Danlos Syndrome in Patients With Congenital Adrenal Hyperplasia
Morissette, R., Chen, W., Perritt, A. F., Dreiling, J. L., Arai, A. E., Sachdev, V., Hannoush, H., Mallappa, A., Xu, Z., McDonnell, N. B., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2232 · Cited by 68 · see citing works
“Normal collagen fibril deposition in connective tissue is essential for the collagenous matrix integrity and defects lead to Ehlers Danlos syndrome (EDS), a hereditary connective tissue disorder (4).”
BackgroundEhlers–Danlos syndrome: A showcase of conditions that lead to understanding matrix biology
Byers, P. H., & Murray, M. L. (2014) · Matrix Biology · doi:10.1016/j.matbio.2013.07.005 · Cited by 68 · see citing works
“…deficiency and EDS due to a contiguous gene deletion that included the gene TNXB. Subsequent studies in mouse knock-outs (Tnxb−/−) suggested that tenascin X likely plays a role in collagen deposition but not synthesis (Mao et al., 2002), which may differ through development (Egging et al., 2006).”
BackgroundTNXB mutations can cause vesicoureteral reflux.
Gbadegesin, R., Brophy, P., Adeyemo, A., Hall, G., Gupta, I., Hains, D., Bartkowiak, B., Rabinovich, C., Chandrasekharappa, S., Homstad, A., et al. (2013) · Journal of the American Society of Nephrology · doi:10.1681/asn.2012121148 · Cited by 66 · see citing works
Malfait, F., & Paepe, A. D. (2013) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-7893-1_9 · Cited by 121 · see citing works
Egging, D. F., van Vlijmen‐Willems, I. M. J. J., van Tongeren, T., Schalkwijk, J., & Peeters, A. C. T. M. (2007) · Connective Tissue Research · doi:10.1080/03008200601166160 · Cited by 63 · see citing works
Tenascin-X, Congenital Adrenal Hyperplasia, and the CAH-X Syndrome
Miller, W. L., & Merke, D. P. (2018) · Hormone Research in Paediatrics · doi:10.1159/000481911 · Cited by 61 · see citing works
Molecular and developmental mechanisms of congenital heart valve disease
Lincoln, J., & Yutzey, K. E. (2011) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.20799 · Cited by 61 · see citing works
“Tenascin-X2/2 mice also exhibit hyperextensibility of the skin, characteristic of EDS, but are viable (Mao et al., 2002).”
BackgroundO'Brien, J., Hansen, K. C., Barkan, D., Green, J., & Schedin, P. (2011) · International Journal of Developmental Biology · doi:10.1387/ijdb.113379jo · Cited by 60 · see citing works
“Tenascin-X, another member of the tenascin glycoprotein family, is involved in directing collagen fibril alignment, and has been previously identified as a constituent of nulliparous rat mammary ECM (Mao et al., 2002; Hansen et al., 2009).”
BackgroundZweers, M. C., Dean, W. B., Kuppevelt, T. H. V., Bristow, J. D., & Schalkwijk, J. (2005) · Clinical Genetics · doi:10.1111/j.1399-0004.2005.00401.x · Cited by 58 · see citing works
“Genetically determined deficiency of TNX is associated with the fragmentation of the elastic fibers and reduction of collagen (11, 12).”
BackgroundSelf-citationKatari, S., Wood-Trageser, M., Jiang, H., Kalynchuk, E., Muzumdar, R., Yatsenko, S., & Rajkovic, A. (2015) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2015-1401 · Cited by 55
“10445G T) was not reported previously, and Tnxb mouse knockouts have no reported reproductive phenotype (7).”
BackgroundLévy, P., Ripoche, H., Laurendeau, I., Lazar, V., Ortonne, N., Parfait, B., Leroy, K., Wechsler, J., Salmon, I., Wolkenstein, P., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0182 · Cited by 53 · see citing works
Expression of tenascin-C and its isoforms in the breast
Guttery, D., Shaw, J. A., Lloyd, K., Pringle, J., & Walker, R. A. (2010) · Cancer Metastasis Review · doi:10.1007/s10555-010-9249-9 · Cited by 51 · see citing works
“Other members of the TN family include tenascin-R (TNR or restrictin), which is restricted to the developing and adult nervous system [7, 8]; tenascin-W (TNW) [9], which is found in the ECM of bone, muscle and kidney [10] (also found recently in malignant mammary tumours [10] and postulated to be a marker of activated…”
BackgroundTenascins in fibrotic disorders—from bench to bedside
Kasprzycka, M., Hammarström, C. L., & Haraldsen, G. (2015) · Cell Adhesion & Migration · doi:10.4161/19336918.2014.994901 · Cited by 56 · see citing works
“Mice deficient in tenascin X partly reproduced this phenotype.(30) In vitro studies revealed that tenascin X interacts with fibrillar collagen type I, III and V when they are in native conformation.”
BackgroundThe evolution of tenascins and fibronectin
Adams, J. C., Chiquet-Ehrismann, R., & Tucker, R. (2015) · Cell Adhesion & Migration · doi:10.4161/19336918.2014.970030 · Cited by 50 · see citing works
“, loose skin and hypermobile joints).(23) It has been proposed that the diversity of the teleost fishes is due in part to the selective retention of genes following 3 rounds of whole genome duplication events.”
BackgroundDeficiency of tenascin-X causes a decrease in the level of expression of type VI collagen.
Minamitani, T., Ariga, H., & Matsumoto, K.-I. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.03.002 · Cited by 49 · see citing works
Proteomic Identification of Matrix Metalloproteinase Substrates in the Human Vasculature
Stegemann, C., Didangelos, A., Barallobre‐Barreiro, J., Langley, S. R., Mandal, K., Jahangiri, M., & Mayr, M. (2012) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.112.964452 · Cited by 50 · see citing works
“Tenascin-X is an important regulator of collagen deposition by dermal fibroblasts.(38) In contrast, tenascin-C binds to fibronectin and inhibits cell spreading.”
BackgroundThe Roles of Tenascins in Cardiovascular, Inflammatory, and Heritable Connective Tissue Diseases
Matsumoto, K., & Aoki, H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.609752 · Cited by 57 · see citing works
“The results of a number of studies on abnormalities in mice with targeted deletion in Tnxb (40) and in clEDS patients (26, 41) have suggested structural roles of TNX in tissue integrity (7, 42).”
BackgroundInfluentialTenascin-X increases the stiffness of collagen gels without affecting fibrillogenesis
Margaron, Y., Bostan, L. E., Exposito, J., Malbouyres, M., Trunfio-Sfarghiu, A.-M., Berthier, Y., & Lethias, C. (2010) · Biophysical Chemistry · doi:10.1016/j.bpc.2009.12.011 · Cited by 46 · see citing works
“Mice deficient in TNX partly reproduced this phenotype [3], and fibroblas ts i olated from these mice failed to deposit collagen in cell culture [4].”
BackgroundMatricellular Proteins in the Trabecular Meshwork: Review and Update
Chatterjee, A., Villarreal, G., & Rhee, D. J. (2014) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2014.0013 · Cited by 48 · see citing works
“Mice deficient in tenascin-X, like their human counterparts, exhibit skin hyperextensibility and fragility, with histologically normal-appearing collagen fibrils that are less densely packed.(204) This mouse strain is now recognized as a suitable model for Ehlers–Danlos syndrome.”
BackgroundMatrix metalloproteinase 14 is required for fibrous tissue expansion
Taylor, S. H., Yeung, C., Kalson, N., Lu, Y.-H., Zigrino, P., Starborg, T., Warwood, S., Holmes, D. F., Canty-Laird, E., Mauch, C., et al. (2015) · eLife · doi:10.7554/elife.09345 · Cited by 44
“…with irregular outlines (Danielson et al., 1997), COMP can act as a catalyst for collagen fibril formation (Halasz et al., 2007), PCOLCE enhances the cleavage of procollagen to collagen (Takahara et al., 1994) and mice lacking TNXB have reduced numbers of collagen fibrils (Mao et al., 2002).”
BackgroundThe extracellular matrix glycoprotein tenascin‐X regulates peripheral sensory and motor neurones
Aktar, R., Peiris, M., Fikree, A., Cibert‐Goton, V., Walmsley, M., Tough, I. R., Watanabe, P. D. S., Araújo, E. J. D. A., Mohammed, S. D., Delalande, J., et al. (2018) · The Journal of Physiology · doi:10.1113/jp276300 · Cited by 43 · see citing works
“TNX-deficient mice show musculoskeletal and cutaneous features of hEDS (Mao et al. 2002) while other aspects of physiology remain uninvestigated.”
BackgroundMethodO'Brien, J., Vanderlinden, L., Schedin, P., & Hansen, K. C. (2012) · Journal of Proteome Research · doi:10.1021/pr3003744 · Cited by 40 · see citing works
Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation
Nakahara, H., Hasegawa, A., Otabe, K., Ayabe, F., Matsukawa, T., Onizuka, N., Ito, Y., Ozaki, T., Lotz, M., & Asahara, H. (2013) · Arthritis & Rheumatism · doi:10.1002/art.38020 · Cited by 39 · see citing works
“Studies of cultured dermal fibroblasts showed that fibroblasts from Tnxb / mice failed to deposit type I collagen into cell-associated matrix, although type I collagen synthesis by cells from Tnxb / and wild-type mice was similar (34).”
Petersen, J., & Douglas, J. (2013) · Medical Hypotheses · doi:10.1016/j.mehy.2013.06.005 · Cited by 39 · see citing works
“Subsequently, researchers conducted studies of both TNXBdeficient mice [23,26] and of human populations diagnosed with EDS-HT who displayed serum levels of TNX 50% below those of healthy patients [6,27].”
BackgroundDermal connective tissue development in mice: an essential role for tenascin-X
Egging, D. F., van Vlijmen, I., STARCHER, B. C., Gijssen, Y., Zweers, M. C., Blankevoort, L., Bristow, J., & Schalkwijk, J. (2005) · Cell and Tissue Research · doi:10.1007/s00441-005-0100-5 · Cited by 33 · see citing works
“Of note, the TNX null allele used in our study is on a different (homogenous C57Black6) background than that used by Mao et al. (2002).”
BackgroundMethodResultInfluentialSelf-citationGhali, N., Sobey, G. J., & Burrows, N. (2019) · BMJ · doi:10.1136/bmj.l4966 · Cited by 60 · see citing works
Gravez, B., Tarjus, A., Jiménez-Canino, R., Moghrabi, S. E., Messaoudi, S., de la Rosa, D. Á., & Jaisser, F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073737 · Cited by 37 · see citing works
“Tenascin-X is an essential regulator of collagen deposition by fibroblasts [28] and is up-regulated during fibrosis after tissue injury [27].”
Background
- Authors
- Mao, J. R., Taylor, G., Dean, W. B., Wagner, D. R., Afzal, V., Lotz, J. C., Rubin, E. M., & Bristow, J.
- Affiliations
- University of California, San Francisco (US)
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Bristow, James
- Venue
- Nature Genetics
- Published
- 2002-03-04
- Volume
- 30
- Issue
- 4
- Pages
- 421-425
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2062321035
- Cited by
- 261
- References
- 0
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 10 · 2023: 7 · 2022: 11 · 2021: 16 · 2020: 12 · 2019: 10 · 2018: 10 · 2017: 7 · 2016: 10 · 2015: 14 · 2014: 7 · 2013: 14 · 2012: 13
- FWCI
- 7.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
- Keywords
- tenascin-X, TNXB, Ehlers-Danlos syndrome, collagen deposition, type I collagen, dermal fibroblasts, skin hyperextensibility, connective tissue diseases, extracellular matrix, skin biomechanics, knockout mice
- MeSH terms
- Animals, Collagen, Ehlers-Danlos Syndrome, Exons, Fibroblasts, Humans, Male, Microscopy, Electron, Microscopy, Fluorescence, Models, Genetic, Molecular Sequence Data, Mutation, Phenotype, Plasmids, Recombination, Genetic, Skin Physiological Phenomena, Time Factors, Immunoblotting, Mice, Knockout, Tenascin, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
