tight skin


Gene Symbol: tight skin
Description: fibrillin 1
Alias: AI536462, B430209H23, Fib-1, Tsk, fibrillin-1, tight skin
Species: mouse
Products:     tight skin

Top Publications

  1. Barisic Dujmovic T, Boban I, Adams D, Clark S. Marfan-like skeletal phenotype in the tight skin (Tsk) mouse. Calcif Tissue Int. 2007;81:305-15 pubmed
    ..dominant mutation located on mouse chromosome 2 and is associated with an intragenic duplication of the fibrillin 1 (Fbn1) gene...
  2. Kinsey R, Williamson M, Chaudhry S, Mellody K, McGovern A, Takahashi S, et al. Fibrillin-1 microfibril deposition is dependent on fibronectin assembly. J Cell Sci. 2008;121:2696-704 pubmed publisher
    ..Thus, pericellular microfibril assembly is regulated by fibronectin fibrillogenesis. ..
  3. Neptune E, Frischmeyer P, Arking D, Myers L, Bunton T, Gayraud B, et al. Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat Genet. 2003;33:407-11 pubmed
    ..These data indicate that matrix sequestration of cytokines is crucial to their regulated activation and signaling and that perturbation of this function can contribute to the pathogenesis of disease. ..
  4. Nistala H, Lee Arteaga S, Smaldone S, Siciliano G, Ramirez F. Extracellular microfibrils control osteoblast-supported osteoclastogenesis by restricting TGF{beta} stimulation of RANKL production. J Biol Chem. 2010;285:34126-33 pubmed publisher
  5. Habashi J, Doyle J, Holm T, Aziz H, Schoenhoff F, Bedja D, et al. Angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through ERK antagonism. Science. 2011;332:361-5 pubmed publisher
    ..These data highlight the protective nature of AT2 signaling and potentially inform the choice of therapies in MFS and related disorders...
  6. Ono R, Sengle G, Charbonneau N, Carlberg V, Bachinger H, Sasaki T, et al. Latent transforming growth factor beta-binding proteins and fibulins compete for fibrillin-1 and exhibit exquisite specificities in binding sites. J Biol Chem. 2009;284:16872-81 pubmed publisher
    ..These studies also suggest that the fibulins may affect matrix sequestration of LTBPs, because in vitro interactions between these proteins are competitive. ..
  7. Ng C, Cheng A, Myers L, Martinez Murillo F, Jie C, Bedja D, et al. TGF-beta-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome. J Clin Invest. 2004;114:1586-92 pubmed
  8. Weihrauch D, Xu H, Shi Y, Wang J, Brien J, Jones D, et al. Effects of D-4F on vasodilation, oxidative stress, angiostatin, myocardial inflammation, and angiogenic potential in tight-skin mice. Am J Physiol Heart Circ Physiol. 2007;293:H1432-41 pubmed
    ..b>Tight skin mice (Tsk(-/+)) have a defect in fibrillin-1, resulting in replication of many of the myocardial and vascular ..
  9. Carta L, Smaldone S, Zilberberg L, Loch D, Dietz H, Rifkin D, et al. p38 MAPK is an early determinant of promiscuous Smad2/3 signaling in the aortas of fibrillin-1 (Fbn1)-null mice. J Biol Chem. 2009;284:5630-6 pubmed publisher
    ..Collectively, these findings indicate that improper activation of p38 MAPK is a precursor of constitutive Smad2/3 signaling in the aortic wall of a mouse model of neonatal lethal Marfan syndrome. ..

More Information


  1. Zhang H, Hu W, Ramirez F. Developmental expression of fibrillin genes suggests heterogeneity of extracellular microfibrils. J Cell Biol. 1995;129:1165-76 pubmed
    ..Accordingly, we propose that fibrillin-1 provides mostly force-bearing structural support, whereas fibrillin-2 predominantly regulates the early process of elastic fiber assembly. ..
  2. Xu H, Zaidi M, Struve J, Jones D, Krolikowski J, Nandedkar S, et al. Abnormal fibrillin-1 expression and chronic oxidative stress mediate endothelial mesenchymal transition in a murine model of systemic sclerosis. Am J Physiol Cell Physiol. 2011;300:C550-6 pubmed publisher
    ..The tight-skin (Tsk(-/+)) mouse is a model of SSc that displays many of the cellular features of the clinical disease...
  3. Shi Y, Tu Y, De Maria A, Mecham R, Bassnett S. Development, composition, and structural arrangements of the ciliary zonule of the mouse. Invest Ophthalmol Vis Sci. 2013;54:2504-15 pubmed publisher
    Here, we examined the development, composition, and structural organization of the ciliary zonule of the mouse. Fibrillin 1, a large glycoprotein enriched in force-bearing tissues, is a prominent constituent of the mouse zonule...
  4. Kielty C, Raghunath M, Siracusa L, Sherratt M, Peters R, Shuttleworth C, et al. The Tight skin mouse: demonstration of mutant fibrillin-1 production and assembly into abnormal microfibrils. J Cell Biol. 1998;140:1159-66 pubmed
    Mice carrying the Tight skin (Tsk) mutation harbor a genomic duplication within the fibrillin-1 (Fbn 1) gene that results in a larger than normal in-frame Fbn 1 transcript...
  5. Charbonneau N, Jordan C, Keene D, Lee Arteaga S, Dietz H, Rifkin D, et al. Microfibril structure masks fibrillin-2 in postnatal tissues. J Biol Chem. 2010;285:20242-51 pubmed publisher
    ..Furthermore, documentation of a novel cryptic site present in EGF4 in fibrillin-1 underscores the molecular complexity and tissue-specific differences in microfibril structure. ..
  6. Charbonneau N, Carlson E, Tufa S, Sengle G, Manalo E, Carlberg V, et al. In vivo studies of mutant fibrillin-1 microfibrils. J Biol Chem. 2010;285:24943-55 pubmed publisher
    ..Taken together, these results suggest that perturbation of microfibril structure may underlie one of the major features of the Marfan syndrome: fragmentation of aortic elastic lamellae...
  7. Bona C, Rothfield N. Autoantibodies in scleroderma and tightskin mice. Curr Opin Immunol. 1994;6:931-7 pubmed
    ..In tightskin mice, the scleroderma syndrome is associated with autoimmunity, particularly autoantibodies interacting with scleroderma target antigens. ..
  8. Merk D, Chin J, Dake B, Maegdefessel L, Miller M, Kimura N, et al. miR-29b participates in early aneurysm development in Marfan syndrome. Circ Res. 2012;110:312-24 pubmed publisher
    ..Although TGF-? blockade prevents aneurysms in MFS mouse models, the mechanisms through which excessive TGF-? causes aneurysms remain ill-defined...
  9. Martorana P, van Even P, Gardi C, Lungarella G. A 16-month study of the development of genetic emphysema in tight-skin mice. Am Rev Respir Dis. 1989;139:226-32 pubmed
    The tight-skin (tsk) mouse has been recently proposed as a model of genetically determined emphysema...
  10. Nistala H, Lee Arteaga S, Smaldone S, Siciliano G, Carta L, Ono R, et al. Fibrillin-1 and -2 differentially modulate endogenous TGF-? and BMP bioavailability during bone formation. J Cell Biol. 2010;190:1107-21 pubmed publisher
    ..Together, these findings identify the extracellular microfibrils as critical regulators of bone formation through the modulation of endogenous TGF-? and BMP signaling...
  11. Holm T, Habashi J, Doyle J, Bedja D, Chen Y, Van Erp C, et al. Noncanonical TGF? signaling contributes to aortic aneurysm progression in Marfan syndrome mice. Science. 2011;332:358-61 pubmed publisher
    ..Thus, noncanonical (Smad-independent) TGF? signaling is a prominent driver of aortic disease in MFS mice, and inhibition of the ERK1/2 or JNK1 pathways is a potential therapeutic strategy for the disease...
  12. Carta L, Pereira L, Arteaga Solis E, Lee Arteaga S, Lenart B, Starcher B, et al. Fibrillins 1 and 2 perform partially overlapping functions during aortic development. J Biol Chem. 2006;281:8016-23 pubmed
  13. Siracusa L, McGrath R, Ma Q, Moskow J, Manne J, Christner P, et al. A tandem duplication within the fibrillin 1 gene is associated with the mouse tight skin mutation. Genome Res. 1996;6:300-13 pubmed
    ..The microfibrillar glycoprotein gene, fibrillin 1 (FBN1), on human chromosome 15q, provided a candidate for the Tsk mutation...
  14. Ramirez F. Fibrillln mutations in Marfan syndrome and related phenotypes. Curr Opin Genet Dev. 1996;6:309-15 pubmed
    A casual association has been established between mutations in the fibrillin 1 gene and Marfan syndrome and related phenotypes. Analysis of mutations in these disease types has provided new insights into microfibril assembly and function...
  15. Pereira L, Andrikopoulos K, Tian J, Lee S, Keene D, Ono R, et al. Targetting of the gene encoding fibrillin-1 recapitulates the vascular aspect of Marfan syndrome. Nat Genet. 1997;17:218-22 pubmed
  16. Xiong W, Meisinger T, Knispel R, Worth J, Baxter B. MMP-2 regulates Erk1/2 phosphorylation and aortic dilatation in Marfan syndrome. Circ Res. 2012;110:e92-e101 pubmed publisher
    ..Losartan has been shown to prevent aneurysms in another mouse model of MFS, Fbn1(C1039G/+), through inhibition of the Erk1/2 pathway. However, the role of MMP-2 in MFS and effect of losartan on the lifespan of MFS mice remain unknown...
  17. Cohn R, Van Erp C, Habashi J, Soleimani A, Klein E, Lisi M, et al. Angiotensin II type 1 receptor blockade attenuates TGF-beta-induced failure of muscle regeneration in multiple myopathic states. Nat Med. 2007;13:204-10 pubmed
    ..Moreover, we show TGF-beta-induced failure of muscle regeneration and a similar therapeutic response in a dystrophin-deficient mouse model of Duchenne muscular dystrophy. ..
  18. Ge G, Greenspan D. BMP1 controls TGFbeta1 activation via cleavage of latent TGFbeta-binding protein. J Cell Biol. 2006;175:111-20 pubmed
    ..TGFbeta1 is a potent inducer of ECM formation and of BMP1 expression. Thus, a role for BMP1-like proteinases in TGFbeta1 activation completes a novel fast-forward loop in vertebrate tissue remodeling. ..
  19. Jimenez S, Williams C, Myers J, Bashey R. Increased collagen biosynthesis and increased expression of type I and type III procollagen genes in tight skin (TSK) mouse fibroblasts. J Biol Chem. 1986;261:657-62 pubmed
    The Tight Skin (TSK) mouse is a mutant strain that displays connective tissue abnormalities characterized by excessive accumulation of collagen in skin, subcutaneous tissues, and some internal organs such as the heart...
  20. Gayraud B, Keene D, Sakai L, Ramirez F. New insights into the assembly of extracellular microfibrils from the analysis of the fibrillin 1 mutation in the tight skin mouse. J Cell Biol. 2000;150:667-80 pubmed
    The Tight skin (Tsk) mutation is a duplication of the mouse fibrillin 1 (Fbn1) gene that results in a larger (418 kD) than normal (350 kD) protein; Tsk/+ mice display increased connective tissue, bone overgrowth, and lung emphysema...
  21. Kasturi K, Hatakeyama A, Murai C, Gordon R, Phelps R, Bona C. B-cell deficiency does not abrogate development of cutaneous hyperplasia in mice inheriting the defective fibrillin-1 gene. J Autoimmun. 1997;10:505-17 pubmed
    Tight-skin (TSK) mouse, the experimental model for scleroderma, develops cutaneous hyperplasia, cardiac hypertrophy, pulmonary emphysema and autoimmunity against scleroderma target autoantigens...
  22. Charbonneau N, Dzamba B, Ono R, Keene D, Corson G, Reinhardt D, et al. Fibrillins can co-assemble in fibrils, but fibrillin fibril composition displays cell-specific differences. J Biol Chem. 2003;278:2740-9 pubmed
    ..This surprising finding implicates distinct functions for fibrillin-2 in peripheral nerves, because a unique feature in humans and in mice mutant for fibrillin-2 is joint contractures that resolve over time. ..
  23. Bunton T, Biery N, Myers L, Gayraud B, Ramirez F, Dietz H. Phenotypic alteration of vascular smooth muscle cells precedes elastolysis in a mouse model of Marfan syndrome. Circ Res. 2001;88:37-43 pubmed
    ..This refined understanding of the pathogenesis of vascular disease in Marfan syndrome will facilitate the development of therapeutic strategies. ..
  24. Green M, Sweet H, Bunker L. Tight-skin, a new mutation of the mouse causing excessive growth of connective tissue and skeleton. Am J Pathol. 1976;82:493-512 pubmed
    A new dominant mutation, tight-skin (Tsk), is located on Chromosome 2, two recombination units distal to pallid (pa)...
  25. Saito E, Fujimoto M, Hasegawa M, Komura K, Hamaguchi Y, Kaburagi Y, et al. CD19-dependent B lymphocyte signaling thresholds influence skin fibrosis and autoimmunity in the tight-skin mouse. J Clin Invest. 2002;109:1453-62 pubmed
    The tight-skin (TSK/+) mouse, a genetic model for human systemic sclerosis (SSc), develops cutaneous fibrosis and autoantibodies against SSc-specific target autoantigens...
  26. Akiyama K, Chen C, Wang D, Xu X, Qu C, Yamaza T, et al. Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell. 2012;10:544-55 pubmed publisher
    ..These data therefore demonstrate a previously unrecognized mechanism underlying BMMSC-based immunotherapy involving coupling via FAS/FASL to induce T cell apoptosis. ..
  27. Podowski M, Calvi C, Cheadle C, Tuder R, Biswals S, Neptune E. Complex integration of matrix, oxidative stress, and apoptosis in genetic emphysema. Am J Pathol. 2009;175:84-96 pubmed publisher
    ..We hypothesized that the tight-skin (TSK) mouse, which harbors a spontaneous internal duplication in the microfibrillar glycoprotein fibrillin-1, might show ..
  28. Arteaga Solis E, Gayraud B, Lee S, Shum L, Sakai L, Ramirez F. Regulation of limb patterning by extracellular microfibrils. J Cell Biol. 2001;154:275-81 pubmed
    ..We also demonstrate that the Fbn2- null mutation is allelic to the recessive shaker-with-syndactyly (sy) locus on chromosome 18...
  29. Zacchigna L, Vecchione C, Notte A, Cordenonsi M, Dupont S, Maretto S, et al. Emilin1 links TGF-beta maturation to blood pressure homeostasis. Cell. 2006;124:929-42 pubmed
    ..This study highlights the importance of modulation of TGF-beta availability in the pathogenesis of hypertension. ..
  30. Habashi J, Judge D, Holm T, Cohn R, Loeys B, Cooper T, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006;312:117-21 pubmed
  31. Pereira L, Lee S, Gayraud B, Andrikopoulos K, Shapiro S, Bunton T, et al. Pathogenetic sequence for aneurysm revealed in mice underexpressing fibrillin-1. Proc Natl Acad Sci U S A. 1999;96:3819-23 pubmed
  32. Li X, Pereira L, Zhang H, Sanguineti C, Ramirez F, Bonadio J, et al. Fibrillin genes map to regions of conserved mouse/human synteny on mouse chromosomes 2 and 18. Genomics. 1993;18:667-72 pubmed
    ..In addition, the Fbn-1 gene maps in the vicinity of the gene for a connective tissue disorder on mouse chromosome 2 called Tight-skin (Tsk).
  33. Chung A, Au Yeung K, Sandor G, Judge D, Dietz H, van Breemen C. Loss of elastic fiber integrity and reduction of vascular smooth muscle contraction resulting from the upregulated activities of matrix metalloproteinase-2 and -9 in the thoracic aortic aneurysm in Marfan syndrome. Circ Res. 2007;101:512-22 pubmed
    ..The resulting elastic fiber degeneration with deterioration of the aortic contraction and mechanical properties may explain the pathogenesis of TAA. ..
  34. Saito M, Kurokawa M, Oda M, Oshima M, Tsutsui K, Kosaka K, et al. ADAMTSL6? protein rescues fibrillin-1 microfibril disorder in a Marfan syndrome mouse model through the promotion of fibrillin-1 assembly. J Biol Chem. 2011;286:38602-13 pubmed publisher
    ..These findings also suggest a new therapeutic strategy for the treatment of MFS through ADAMTSL6?-mediated fibrillin-1 microfibril assembly. ..
  35. Le Goff C, Mahaut C, Wang L, Allali S, Abhyankar A, Jensen S, et al. Mutations in the TGF? binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias. Am J Hum Genet. 2011;89:7-14 pubmed publisher
    ..After exome sequencing in GD and AD cases, we selected fibrillin 1 (FBN1) as a candidate gene, even though mutations in this gene have been described in Marfan syndrome, which is ..
  36. Judge D, Biery N, Keene D, Geubtner J, Myers L, Huso D, et al. Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome. J Clin Invest. 2004;114:172-81 pubmed
    ..In keeping with this model, introduction of a WT FBN1 transgene on a heterozygous C1039G background rescues aortic phenotype. ..
  37. Tsutsui K, Manabe R, Yamada T, Nakano I, Oguri Y, Keene D, et al. ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-1 and promotes fibrillin-1 fibril formation. J Biol Chem. 2010;285:4870-82 pubmed publisher
    ..All together, these results indicated that ADAMTSL-6 is a novel microfibril-associated protein that binds directly to fibrillin-1 and promotes fibrillin-1 matrix assembly. ..
  38. Levi Schaffer F, Nagler A, Slavin S, Knopov V, Pines M. Inhibition of collagen synthesis and changes in skin morphology in murine graft-versus-host disease and tight skin mice: effect of halofuginone. J Invest Dermatol. 1996;106:84-8 pubmed
    ..was evaluated in two in vivo models of scleroderma: the murine chronic graft-versus-host disease (cGvHD) and the tight skin mouse...
  39. Yin W, Smiley E, Germiller J, Sanguineti C, Lawton T, Pereira L, et al. Primary structure and developmental expression of Fbn-1, the mouse fibrillin gene. J Biol Chem. 1995;270:1798-806 pubmed
    ..A survey of expression in mouse embryo tissues is consistent with this hypothesis and suggests two novel functions for fibrillin-associated microfibrils in non-elastic connective tissues. ..
  40. Omens J, Rockman H, Covell J. Passive ventricular mechanics in tight-skin mice. Am J Physiol. 1994;266:H1169-76 pubmed
    ..Accordingly, we studied passive ventricular mechanics in the tight-skin (TSk) mouse, a mutant strain known to have increased cardiac collagen...
  41. Smaldone S, Bigarella C, del Solar M, Ghaffari S, Ramirez F. Fibrillin-1 microfibrils influence adult bone marrow hematopoiesis. Matrix Biol. 2016;52-54:88-94 pubmed publisher
    ..The distinct outcomes of these pharmacological interventions strongly suggest that fibrillin-1 differentially modulates TGFβ activity in HSC vs. erythroid niches. ..
  42. Suda N, Moriyama K, Ganburged G. Effect of angiotensin II receptor blocker on experimental periodontitis in a mouse model of Marfan syndrome. Infect Immun. 2013;81:182-8 pubmed publisher
    ..This study suggests that ARB can prevent the severe periodontitis frequently seen in Marfan syndrome...
  43. Smaldone S, Clayton N, del Solar M, Pascual G, Cheng S, Wentworth B, et al. Fibrillin-1 Regulates Skeletal Stem Cell Differentiation by Modulating TGFβ Activity Within the Marrow Niche. J Bone Miner Res. 2016;31:86-97 pubmed publisher
    ..Collectively, our findings show that fibrillin-1 regulates MSC activity by modulating TGFβ bioavailability within the microenvironment of marrow niches. ..
  44. Ito S, Bartolak Suki E, Shipley J, Parameswaran H, Majumdar A, Suki B. Early emphysema in the tight skin and pallid mice: roles of microfibril-associated glycoproteins, collagen, and mechanical forces. Am J Respir Cell Mol Biol. 2006;34:688-94 pubmed
    The nature of the development of emphysema in the tight skin (Tsk) and the pallid (Pa) mice are not well understood...
  45. Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, et al. Asprosin, a Fasting-Induced Glucogenic Protein Hormone. Cell. 2016;165:566-79 pubmed publisher
    ..Asprosin represents a glucogenic protein hormone, and therapeutically targeting it may be beneficial in type II diabetes and metabolic syndrome. ..
  46. Lee L, Cui J, Cua M, Esfandiarei M, Sheng X, Chui W, et al. Aortic and Cardiac Structure and Function Using High-Resolution Echocardiography and Optical Coherence Tomography in a Mouse Model of Marfan Syndrome. PLoS ONE. 2016;11:e0164778 pubmed publisher
  47. Williams T, Williams M, Kuick R, Misek D, McDonagh K, Hanash S, et al. Candidate downstream regulated genes of HOX group 13 transcription factors with and without monomeric DNA binding capability. Dev Biol. 2005;279:462-80 pubmed
    ..Our results suggest that HOX protein-protein interactions without direct HOX DNA-binding may play a larger role in HOX transcriptional regulation than generally assumed, and DNA-binding appears critical for repression. ..
  48. Agren M, Mertz P. Are excessive granulation tissue formation and retarded wound contraction due to decreased collagenase activity in wounds in tight-skin mice?. Br J Dermatol. 1994;131:337-40 pubmed
    ..Furthermore, this animal would model may prove useful in the understanding of the pathogenesis, and in exploration of treatment, of excessive granulation tissue formation during wound healing. ..
  49. Gerber E, Gallo E, Fontana S, Davis E, Wigley F, Huso D, et al. Integrin-modulating therapy prevents fibrosis and autoimmunity in mouse models of scleroderma. Nature. 2013;503:126-30 pubmed publisher
    ..These results show that alterations in cell-matrix interactions are sufficient to initiate and sustain inflammatory and pro-fibrotic programmes and highlight new therapeutic strategies. ..
  50. Sun J, Chen H, Chen C, Whitsett J, Mishina Y, Bringas P, et al. Prenatal lung epithelial cell-specific abrogation of Alk3-bone morphogenetic protein signaling causes neonatal respiratory distress by disrupting distal airway formation. Am J Pathol. 2008;172:571-82 pubmed publisher
    ..Therefore, our data suggest that deficiency of appropriate BMP signaling in lung epithelial cells results in prenatal lung malformation, neonatal atelectasis, and respiratory failure. ..
  51. Shahan K, Gilmartin M, Derman E. Nucleotide sequences of liver, lachrymal, and submaxillary gland mouse major urinary protein mRNAs: mosaic structure and construction of panels of gene-specific synthetic oligonucleotide probes. Mol Cell Biol. 1987;7:1938-46 pubmed
    ..Shahan, M. Denaro, M. Gilmartin, Y. Shi, and E. Derman, Mol. Cell. Biol. 7:1947-1954, 1987), to characterize the expression of MUP genes I through V. ..
  52. Franken R, Hibender S, den Hartog A, Radonic T, de Vries C, Zwinderman A, et al. No beneficial effect of general and specific anti-inflammatory therapies on aortic dilatation in Marfan mice. PLoS ONE. 2014;9:e107221 pubmed publisher
    ..Currently, the most promising therapeutic drug in Marfan syndrome is losartan, by blocking the angiotensin II receptor type 1 and thereby inhibiting pSmad2 signaling. ..
  53. Van der Donckt C, Roth L, Vanhoutte G, Blockx I, Bink D, Ritz K, et al. Fibrillin-1 impairment enhances blood-brain barrier permeability and xanthoma formation in brains of apolipoprotein E-deficient mice. Neuroscience. 2015;295:11-22 pubmed publisher
    ..As a consequence, lipoproteins can enter the brain, resulting in accelerated formation of xanthomas. ..
  54. Lemaire R, Korn J, Schiemann W, Lafyatis R. Fibulin-2 and fibulin-5 alterations in tsk mice associated with disorganized hypodermal elastic fibers and skin tethering. J Invest Dermatol. 2004;123:1063-9 pubmed
    The Tight skin (Tsk) mouse is an important model of skin fibrosis that occurs in systemic sclerosis. These mice develop skin tethering and thickening associated with expression of a mutant fibrillin-1 gene...
  55. Guo G, Munoz Garcia B, Ott C, Grünhagen J, Mousa S, Pletschacher A, et al. Antagonism of GxxPG fragments ameliorates manifestations of aortic disease in Marfan syndrome mice. Hum Mol Genet. 2013;22:433-43 pubmed publisher
    ..Moreover, the results of the current study suggest that antagonism of the effects of GxxPG fragments may be a fruitful therapeutic strategy in MFS. ..
  56. Schiavinato A, Keene D, Wohl A, Corallo D, Colombatti A, Wagener R, et al. Targeting of EMILIN-1 and EMILIN-2 to Fibrillin Microfibrils Facilitates their Incorporation into the Extracellular Matrix. J Invest Dermatol. 2016;136:1150-1160 pubmed publisher
    ..The addition of EMILINs to the ligand repertoire of fibrillin strengthens the concept of fibrillin microfibrils as extracellular scaffolds integrating cellular force transmission and growth factor bioactivity. ..
  57. Keil M, Lungarella G, Cavarra E, van Even P, Martorana P. A scanning electron microscopic investigation of genetic emphysema in tight-skin, pallid, and beige mice, three different C57 BL/6J mutants. Lab Invest. 1996;74:353-62 pubmed
    Three mutants of the C57 BL/6J strain, i.e., the tight-skin (Tsk), pallid (pa), and beige (bg) mice have been reported to develop spontaneous emphysema...
  58. Pablos J, Carreira P, Serrano L, Del Castillo P, Gomez Reino J. Apoptosis and proliferation of fibroblasts during postnatal skin development and scleroderma in the tight-skin mouse. J Histochem Cytochem. 1997;45:711-9 pubmed
    Tight-skin (Tsk) is a dominant gene mutation that causes a fibrotic skin disease in mice, similar to human scleroderma...
  59. Saito S, Nishimura H, Phelps R, Wolf I, Suzuki M, Honjo T, et al. Induction of skin fibrosis in mice expressing a mutated fibrillin-1 gene. Mol Med. 2000;6:825-36 pubmed
    b>Tight skin mice (TSK) bear a mutated Fibrillin-1 (Fbn-1) gene. Genetic studies show that the TSK mutation is closely associated with the Fbn-1 locus (0-0.7 cM)...
  60. Dale M, Fitzgerald M, Liu Z, Meisinger T, Karpisek A, Purcell L, et al. Premature aortic smooth muscle cell differentiation contributes to matrix dysregulation in Marfan Syndrome. PLoS ONE. 2017;12:e0186603 pubmed publisher
    ..This study indicates that an early phenotypic switch appears to be associated with initiation of important metabolic changes in SMCs that contribute to subsequent pathology in MFS. ..
  61. Doyle J, Doyle A, Wilson N, Habashi J, Bedja D, Whitworth R, et al. A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome. elife. 2015;4: pubmed publisher
    ..Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents. ..
  62. Kasturi K, Daian C, Saitoh Y, Muryoi T, Bona C. Tight-skin mouse autoantibody repertoire: analysis of VH and VK gene usage. Mol Immunol. 1993;30:969-78 pubmed
    In the previous studies we have shown that tight-skin (TSK) mouse is an experimental model for systemic sclerosis. This mutant mouse develops autoantibodies specific for scleroderma target antigens...
  63. Chen C, Akiyama K, Yamaza T, You Y, Xu X, Li B, et al. Telomerase governs immunomodulatory properties of mesenchymal stem cells by regulating FAS ligand expression. EMBO Mol Med. 2014;6:322-34 pubmed publisher
  64. Xu H, Krolikowski J, Jones D, Ge Z, Pagel P, Pritchard K, et al. 4F decreases IRF5 expression and activation in hearts of tight skin mice. PLoS ONE. 2012;7:e52046 pubmed publisher
    The apoAI mimetic 4F was designed to inhibit atherosclerosis by improving HDL. We reported that treating tight skin (Tsk(-/+)) mice, a model of systemic sclerosis (SSc), with 4F decreases inflammation and restores angiogenic potential in ..
  65. Bashey R, Philips N, Insinga F, Jimenez S. Increased collagen synthesis and increased content of type VI collagen in myocardium of tight skin mice. Cardiovasc Res. 1993;27:1061-5 pubmed
    The tight skin mouse (TSK) is a mutant strain characterised by excessive collagen accumulation in skin and some internal organs such as the heart...
  66. Carta L, Wagenseil J, Knutsen R, Mariko B, Faury G, Davis E, et al. Discrete contributions of elastic fiber components to arterial development and mechanical compliance. Arterioscler Thromb Vasc Biol. 2009;29:2083-9 pubmed publisher
    ..These results demonstrate that elastin and fibrillin-1 have both differential and complementary roles in arterial wall formation and function, and advance our knowledge of the structural determinants of vascular physiology and disease. ..
  67. Gould R, Sinha R, Aziz H, Rouf R, Dietz H, Judge D, et al. Multi-scale biomechanical remodeling in aging and genetic mutant murine mitral valve leaflets: insights into Marfan syndrome. PLoS ONE. 2012;7:e44639 pubmed publisher
    ..Decoupling of local cell-matrix deformation kinematics with global tissue stretch may be an important mechanism of normal and pathological biomechanical remodeling in valves. ..
  68. Samuel C, Sakai L, Amento E. Relaxin regulates fibrillin 2, but not fibrillin 1, mRNA and protein expression by human dermal fibroblasts and murine fetal skin. Arch Biochem Biophys. 2003;411:47-55 pubmed
    ..We have found that relaxin specifically inhibits a microfibril component, fibrillin 2 (FBN2), without affecting fibrillin 1 (FBN1)...
  69. Summers K, Raza S, van Nimwegen E, Freeman T, Hume D. Co-expression of FBN1 with mesenchyme-specific genes in mouse cell lines: implications for phenotypic variability in Marfan syndrome. Eur J Hum Genet. 2010;18:1209-15 pubmed publisher
    ..Promoter analysis of this gene set identified several candidate transcriptional regulators. Genes within this co-expressed cluster are candidate genetic modifiers for Marfan syndrome and for other connective tissue diseases...