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Gene Review

Fbn1  -  fibrillin 1

Mus musculus

Synonyms: AI536462, B430209H23, Fbn-1, Fib-1, Fibrillin-1, ...
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Disease relevance of Fbn1


Psychiatry related information on Fbn1

  • Mouse lemurs remained torpid between 1.7-8.9 h with a daily mean of 3.4 h, and their Tsk s fell to a minimum of 18.8 degrees C. Mean home ranges of mouse lemurs which remained normothermic were similar in the rainy and dry season [6].

High impact information on Fbn1

  • Aged mice deficient in fibrillin-1 develop destructive emphysema consistent with the view that early developmental perturbations can predispose to late-onset, seemingly acquired phenotypes [4].
  • To investigate the pathogenesis of genetically imposed emphysema, we analyzed the lung phenotype of mice deficient in fibrillin-1, an accepted model of Marfan syndrome [4].
  • The vascular phenotype of MFS results from mutations in fibrillin-1 (FBN1), the major constituent of extracellular microfibrils [7].
  • Targetting of the gene encoding fibrillin-1 recapitulates the vascular aspect of Marfan syndrome [7].
  • Here we report a gene-targetting experiment in mice that indicates that fibrillin-1 microfibrils are predominantly engaged in tissue homeostasis rather than elastic matrix assembly [7].

Chemical compound and disease context of Fbn1


Biological context of Fbn1

  • We now demonstrate that the Tsk chromosome harbors a 30- to 40-kb genomic duplication within the Fbn1 gene that results in a larger than normal in-frame Fbn1 transcript [11].
  • However, virtually all Fbn1-/-;Fbn2-/- embryos and about half of the Fbn1+/-;Fbn2-/- embryos died in utero and displayed a significantly more severe vascular phenotype than Fbn1-/- mice [3].
  • To elucidate the contribution of fibrillin-rich microfibrils to organogenesis, we have examined the vascular phenotype of a newly created strain of mice that completely lacks fibrillin-1 and the consequences of combined deficiency of fibrillins 1 and 2 on tissue formation [3].
  • Of mice and Marfan: genetic linkage analyses of the fibrillin genes, Fbn1 and Fbn2, in the mouse genome [12].
  • Tsk/Tsk cells produce only mutated fibrillin-1 which arises from mRNA containing an in-frame duplication of exons 17-40 [13].

Anatomical context of Fbn1


Associations of Fbn1 with chemical compounds


Enzymatic interactions of Fbn1

  • We found that loss of fibrillin-1 deposition promotes the production of intracellular reactive oxygen species and abnormal accumulation of phosphorylated TGF-beta-activated kinase 1 and p38 MAPK, in addition to increasing the levels of endogenous phospho-Smad2 [20].

Regulatory relationships of Fbn1


Other interactions of Fbn1

  • Moreover, MEF cells expressing tsk-Fbn1 showed increased MAGP-2 matrix [2].
  • Restriction fragment length polymorphisms (RFLPs) between the progenitors of an interspecific backcross involving AEJ/Gn and Mus spretus mice were used to establish the segregation patterns of the murine homologs, Fbn1 and Fbn2, in the backcross progeny [12].
  • The results position Fbn1 between the B2m and Illa genes on mouse Chromosome (Chr) 2 and establish its candidacy for the Tight skin (Tsk) mutation [12].
  • Mutant fibrillin 1 from tight skin mice increases extracellular matrix incorporation of microfibril-associated glycoprotein 2 and type I collagen [2].
  • Resultant mdx/Tsk double-mutant mice were then examined functionally, biochemically, and histologically [17].

Analytical, diagnostic and therapeutic context of Fbn1


  1. New insights into the assembly of extracellular microfibrils from the analysis of the fibrillin 1 mutation in the tight skin mouse. Gayraud, B., Keene, D.R., Sakai, L.Y., Ramirez, F. J. Cell Biol. (2000) [Pubmed]
  2. Mutant fibrillin 1 from tight skin mice increases extracellular matrix incorporation of microfibril-associated glycoprotein 2 and type I collagen. Lemaire, R., Farina, G., Kissin, E., Shipley, J.M., Bona, C., Korn, J.H., Lafyatis, R. Arthritis Rheum. (2004) [Pubmed]
  3. Fibrillins 1 and 2 perform partially overlapping functions during aortic development. Carta, L., Pereira, L., Arteaga-Solis, E., Lee-Arteaga, S.Y., Lenart, B., Starcher, B., Merkel, C.A., Sukoyan, M., Kerkis, A., Hazeki, N., Keene, D.R., Sakai, L.Y., Ramirez, F. J. Biol. Chem. (2006) [Pubmed]
  4. Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Neptune, E.R., Frischmeyer, P.A., Arking, D.E., Myers, L., Bunton, T.E., Gayraud, B., Ramirez, F., Sakai, L.Y., Dietz, H.C. Nat. Genet. (2003) [Pubmed]
  5. B-cell deficiency does not abrogate development of cutaneous hyperplasia in mice inheriting the defective fibrillin-1 gene. Kasturi, K.N., Hatakeyama, A., Murai, C., Gordon, R., Phelps, R.G., Bona, C.A. J. Autoimmun. (1997) [Pubmed]
  6. Daily energy expenditure of the grey mouse lemur (Microcebus murinus): a small primate that uses torpor. Schmid, J., Speakman, J.R. J. Comp. Physiol. B, Biochem. Syst. Environ. Physiol. (2000) [Pubmed]
  7. Targetting of the gene encoding fibrillin-1 recapitulates the vascular aspect of Marfan syndrome. Pereira, L., Andrikopoulos, K., Tian, J., Lee, S.Y., Keene, D.R., Ono, R., Reinhardt, D.P., Sakai, L.Y., Biery, N.J., Bunton, T., Dietz, H.C., Ramirez, F. Nat. Genet. (1997) [Pubmed]
  8. Expression of a mutant human fibrillin allele upon a normal human or murine genetic background recapitulates a Marfan cellular phenotype. Eldadah, Z.A., Brenn, T., Furthmayr, H., Dietz, H.C. J. Clin. Invest. (1995) [Pubmed]
  9. Role of fibrillin-1 in hypertensive and diabetic glomerular disease. Hartner, A., Schaefer, L., Porst, M., Cordasic, N., Gabriel, A., Klanke, B., Reinhardt, D.P., Hilgers, K.F. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  10. Immunohistochemical evaluation of conjunctival fibrillin-1 in Marfan syndrome. Ganesh, A., Smith, C., Chan, W., Unger, S., Quercia, N., Godfrey, M., Kraft, S., Buncic, R., Levin, A. Arch. Ophthalmol. (2006) [Pubmed]
  11. A tandem duplication within the fibrillin 1 gene is associated with the mouse tight skin mutation. Siracusa, L.D., McGrath, R., Ma, Q., Moskow, J.J., Manne, J., Christner, P.J., Buchberg, A.M., Jimenez, S.A. Genome Res. (1996) [Pubmed]
  12. Of mice and Marfan: genetic linkage analyses of the fibrillin genes, Fbn1 and Fbn2, in the mouse genome. Goldstein, C., Liaw, P., Jimenez, S.A., Buchberg, A.M., Siracusa, L.D. Mamm. Genome (1994) [Pubmed]
  13. Extracellular matrix containing mutated fibrillin-1 (Fbn1) down regulates Col1a1, Col1a2, Col3a1, Col5a1, and Col5a2 mRNA levels in Tsk/+ and Tsk/Tsk embryonic fibroblasts. Christner, P.J., Ayitey, S. Amino Acids (2006) [Pubmed]
  14. Microfibril-associated glycoprotein-2 interacts with fibrillin-1 and fibrillin-2 suggesting a role for MAGP-2 in elastic fiber assembly. Penner, A.S., Rock, M.J., Kielty, C.M., Shipley, J.M. J. Biol. Chem. (2002) [Pubmed]
  15. Developmental expression of fibrillin genes suggests heterogeneity of extracellular microfibrils. Zhang, H., Hu, W., Ramirez, F. J. Cell Biol. (1995) [Pubmed]
  16. TGF-beta1 binding protein-like modules of fibrillin-1 and -2 mediate integrin-dependent cell adhesion. D'Arrigo, C., Burl, S., Withers, A.P., Dobson, H., Black, C., Boxer, M. Connect. Tissue Res. (1998) [Pubmed]
  17. Duchenne-like myopathy in double-mutant mdx mice expressing exaggerated mast cell activity. Granchelli, J.A., Pollina, C., Hudecki, M.S. J. Neurol. Sci. (1995) [Pubmed]
  18. Fibrillin-1 and -2 contain heparin-binding sites important for matrix deposition and that support cell attachment. Ritty, T.M., Broekelmann, T.J., Werneck, C.C., Mecham, R.P. Biochem. J. (2003) [Pubmed]
  19. Activation and interaction with protein kinase C of a cytoplasmic tyrosine kinase, Itk/Tsk/Emt, on Fc epsilon RI cross-linking on mast cells. Kawakami, Y., Yao, L., Tashiro, M., Gibson, S., Mills, G.B., Kawakami, T. J. Immunol. (1995) [Pubmed]
  20. p38 MAPK is an early determinant of promiscuous Smad2/3 signaling in the aortas of fibrillin-1 (Fbn1)-null mice. Carta, L., Smaldone, S., Zilberberg, L., Loch, D., Dietz, H.C., Rifkin, D.B., Ramirez, F. J. Biol. Chem. (2009) [Pubmed]
  21. TGF-beta-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome. Ng, C.M., Cheng, A., Myers, L.A., Martinez-Murillo, F., Jie, C., Bedja, D., Gabrielson, K.L., Hausladen, J.M., Mecham, R.P., Judge, D.P., Dietz, H.C. J. Clin. Invest. (2004) [Pubmed]
  22. Regulation of fibrillin-1 by biglycan and decorin is important for tissue preservation in the kidney during pressure-induced injury. Schaefer, L., Mihalik, D., Babelova, A., Krzyzankova, M., Gröne, H.J., Iozzo, R.V., Young, M.F., Seidler, D.G., Lin, G., Reinhardt, D.P., Schaefer, R.M. Am. J. Pathol. (2004) [Pubmed]
  23. Fibrillin-1 regulates mesangial cell attachment, spreading, migration and proliferation. Porst, M., Plank, C., Bieritz, B., Konik, E., Fees, H., Dötsch, J., Hilgers, K.F., Reinhardt, D.P., Hartner, A. Kidney Int. (2006) [Pubmed]
  24. Viscoelastic properties of skin in Mov-13 and Tsk mice. Del Prete, Z., Antoniucci, S., Hoffman, A.H., Grigg, P. Journal of biomechanics. (2004) [Pubmed]
  25. Microfibrils at basement membrane zones interact with perlecan via fibrillin-1. Tiedemann, K., Sasaki, T., Gustafsson, E., Göhring, W., Bätge, B., Notbohm, H., Timpl, R., Wedel, T., Schlötzer-Schrehardt, U., Reinhardt, D.P. J. Biol. Chem. (2005) [Pubmed]
  26. Assembly of epithelial cell fibrillins. Dzamba, B.J., Keene, D.R., Isogai, Z., Charbonneau, N.L., Karaman-Jurukovska, N., Simon, M., Sakai, L.Y. J. Invest. Dermatol. (2001) [Pubmed]
  27. Fibrillin genes map to regions of conserved mouse/human synteny on mouse chromosomes 2 and 18. Li, X., Pereira, L., Zhang, H., Sanguineti, C., Ramirez, F., Bonadio, J., Francke, U. Genomics (1993) [Pubmed]
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