tissue inhibitor of metalloproteinase 3

Summary

Summary: A member of the family of tissue inhibitor of metalloproteinases. Mutations of the gene for TIMP3 PROTEIN causes Sorsby fundus dystrophy.

Top Publications

  1. Federici M, Hribal M, Menghini R, Kanno H, Marchetti V, Porzio O, et al. Timp3 deficiency in insulin receptor-haploinsufficient mice promotes diabetes and vascular inflammation via increased TNF-alpha. J Clin Invest. 2005;115:3494-505 pubmed
    ..In insulin receptor heterozygous (Insr+/-) mice, we identified the deficiency of tissue inhibitor of metalloproteinase 3 (Timp3, an inhibitor of both TNF-alpha-converting enzyme [TACE] and MMPs) as a common bond ..
  2. Smookler D, Mohammed F, Kassiri Z, Duncan G, Mak T, Khokha R. Tissue inhibitor of metalloproteinase 3 regulates TNF-dependent systemic inflammation. J Immunol. 2006;176:721-5 pubmed
    ..TNF shedding is mediated by TNF-alpha converting enzyme, which is selectively inhibited by the tissue inhibitor of metalloproteinase 3 (TIMP3)...
  3. Bond M, Murphy G, Bennett M, Newby A, Baker A. Tissue inhibitor of metalloproteinase-3 induces a Fas-associated death domain-dependent type II apoptotic pathway. J Biol Chem. 2002;277:13787-95 pubmed
    ..Taken together, these results indicate that TIMP-3 overexpression induces a type II apoptotic pathway initiated via a Fas-associated death domain-dependent mechanism. ..
  4. Jacobson S, Cideciyan A, Bennett J, Kingsley R, Sheffield V, Stone E. Novel mutation in the TIMP3 gene causes Sorsby fundus dystrophy. Arch Ophthalmol. 2002;120:376-9 pubmed
  5. Fata J, Chaudhary V, Khokha R. Cellular turnover in the mammary gland is correlated with systemic levels of progesterone and not 17beta-estradiol during the estrous cycle. Biol Reprod. 2001;65:680-8 pubmed
    ..We propose that the cyclical turnover of epithelial cells within the adult mammary tissue is a sum of spatial and functional coordination of hormonal and matrix regulatory factors. ..
  6. Weber B, Lin B, White K, Kohler K, Soboleva G, Herterich S, et al. A mouse model for Sorsby fundus dystrophy. Invest Ophthalmol Vis Sci. 2002;43:2732-40 pubmed
    ..In addition, our immunolabeling studies and biochemical data support a model proposing that site-specific excess rather than absence or deficiency of functional Timp3 may be the primary consequence of the known Timp3 mutations. ..
  7. Li Z, Clarke M, Barker M, McKie N. TIMP3 mutation in Sorsby's fundus dystrophy: molecular insights. Expert Rev Mol Med. 2005;7:1-15 pubmed
    ..We also discuss briefly how, despite the lack of inherited mutations in the structural gene, the TIMP3 protein might play a role in the onset and progression of AMD. ..
  8. Gagnon J, Shaker S, Primeau M, Hurtubise A, Momparler R. Interaction of 5-aza-2'-deoxycytidine and depsipeptide on antineoplastic activity and activation of 14-3-3sigma, E-cadherin and tissue inhibitor of metalloproteinase 3 expression in human breast carcinoma cells. Anticancer Drugs. 2003;14:193-202 pubmed
    ..we investigated the effect of these drugs on the activation of the 14-3-3sigma, E-cadherin and tissue inhibitor of metalloproteinase 3 (TIMP3) cancer-related genes, which were reported to be silenced by aberrant methylation in many ..
  9. Arris C, Bevitt D, Mohamed J, Li Z, Langton K, Barker M, et al. Expression of mutant and wild-type TIMP3 in primary gingival fibroblasts from Sorsby's fundus dystrophy patients. Biochim Biophys Acta. 2003;1638:20-8 pubmed
    ..These cell lines were grown in culture to study expression of the wild-type and mutant tissue inhibitor of metalloproteinase 3 (TIMP3) alleles from a normal diploid cell type...

More Information

Publications62

  1. Karan D, Lin F, Bryan M, Ringel J, Moniaux N, Lin M, et al. Expression of ADAMs (a disintegrin and metalloproteases) and TIMP-3 (tissue inhibitor of metalloproteinase-3) in human prostatic adenocarcinomas. Int J Oncol. 2003;23:1365-71 pubmed
    ..These results suggest that an inverse expression pattern of ADAM-17/TACE and TIMP-3, and the regulation of ADAMs with DHT might play an important role in the pathogenesis of prostate cancer. ..
  2. Miyazaki T, Kato H, Nakajima M, Faried A, Takita J, Sohda M, et al. An immunohistochemical study of TIMP-3 expression in oesophageal squamous cell carcinoma. Br J Cancer. 2004;91:1556-60 pubmed
    ..This makes the prognosis for patients with cancer that has lost TIMP-3 significantly less favourable than that for patients with cancer that has maintained TIMP-3. ..
  3. Nagel H, Laskawi R, Wahlers A, Hemmerlein B. Expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitors TIMP-1, -2, and -3 in benign and malignant tumours of the salivary gland. Histopathology. 2004;44:222-31 pubmed
    ..Our findings suggest a disturbed balance between MMP and TIMP in malignant salivary gland tumours. MMP-2 expression in particular seems to be related to the invasive properties and the malignant potential of these tumours. ..
  4. Troeberg L, Fushimi K, Scilabra S, Nakamura H, Dive V, Thøgersen I, et al. The C-terminal domains of ADAMTS-4 and ADAMTS-5 promote association with N-TIMP-3. Matrix Biol. 2009;28:463-9 pubmed publisher
    ..5-fold better K(i) value for full-length ADAMTS-5 than for the catalytic and disintegrin domain alone. We propose that the C-terminal domains of the enzymes affect the structure around the active site, favouring interaction with TIMP-3. ..
  5. Lee M, Maskos K, Knauper V, Dodds P, Murphy G. Mapping and characterization of the functional epitopes of tissue inhibitor of metalloproteinases (TIMP)-3 using TIMP-1 as the scaffold: a new frontier in TIMP engineering. Protein Sci. 2002;11:2493-503 pubmed
    ..Most importantly, our findings confirm that the individual characteristics of TIMP could be transplanted from one variant to another. ..
  6. Federici M, Menghini R, Mauriello A, Hribal M, Ferrelli F, Lauro D, et al. Insulin-dependent activation of endothelial nitric oxide synthase is impaired by O-linked glycosylation modification of signaling proteins in human coronary endothelial cells. Circulation. 2002;106:466-72 pubmed
    ..Our data show that hyperglycemia, through the hexosamine pathway, impairs activation of the IR/IRS/PI3-K/Akt pathway, resulting in deregulation of eNOS activity. ..
  7. Tunuguntla R, Ripley D, Sang Q, Chegini N. Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinases TIMP-3 and -4 in benign endometrium and endometrial cancer. Gynecol Oncol. 2003;89:453-9 pubmed
    ..MMP-26 and TIMP-4 are expressed in endometrium and endometrial carcinoma and their elevated expression and correlation with myometrial invasion suggests that MMP-26 and TIMP-4 may play a key role in endometrial tumor progression. ..
  8. Ueki T, Walter K, Skinner H, Jaffee E, Hruban R, Goggins M. Aberrant CpG island methylation in cancer cell lines arises in the primary cancers from which they were derived. Oncogene. 2002;21:2114-7 pubmed
    ..92, P<0.0001). We conclude that most of the DNA methylation of tumor suppressor genes observed in cancer cell lines is present in the primary carcinomas from which they were derived. ..
  9. Fata J, Leco K, Voura E, Yu H, Waterhouse P, Murphy G, et al. Accelerated apoptosis in the Timp-3-deficient mammary gland. J Clin Invest. 2001;108:831-41 pubmed
    ..The physiological relevance of TIMP-3 became apparent as Timp-3(-/-) dams failed to reestablish lactation after brief cessation of suckling. Thus, TIMP-3 is a critical epithelial survival factor during mammary gland involution. ..
  10. Mylona E, Magkou C, Giannopoulou I, Agrogiannis G, Markaki S, Keramopoulos A, et al. Expression of tissue inhibitor of matrix metalloproteinases (TIMP)-3 protein in invasive breast carcinoma: relation to tumor phenotype and clinical outcome. Breast Cancer Res. 2006;8:R57 pubmed
  11. Peters A, Young M, Miller J. Optical coherence tomography for assessing disease progression in sorsby fundus dystrophy. Retina. 2006;26:1082-4 pubmed
  12. Smith E, De Young N, Tian Z, Caruso M, Ruszkiewicz A, Liu J, et al. Methylation of TIMP3 in esophageal squamous cell carcinoma. World J Gastroenterol. 2008;14:203-10 pubmed
    To measure the frequency of DNA methylation of the tissue inhibitor of metalloproteinase 3 (TIMP3) promoter and relate this to any change of gene expression in esophageal squamous cell carcinoma in patients from a region of high ..
  13. Wang W, Ge G, Lim N, Nagase H, Greenspan D. TIMP-3 inhibits the procollagen N-proteinase ADAMTS-2. Biochem J. 2006;398:515-9 pubmed
    ..In contrast, TIMP-3 is demonstrated to inhibit ADAMTS-2 in vitro with apparent Ki values of 160 and 602 nM, in the presence of heparin or without respectively; and TIMP-3 is shown to inhibit procollagen processing by cells. ..
  14. Bai Y, Yi J, Li J, Sui H. Clinicopathologic significance of BAG1 and TIMP3 expression in colon carcinoma. World J Gastroenterol. 2007;13:3883-5 pubmed
    To explore the expression of BAG1 and tissue inhibitor of metalloproteinase 3 (TIMP3) in colon carcinoma and their correlation and clinicopathologic significance...
  15. Monroy A, Kamath S, Chavez A, Centonze V, Veerasamy M, Barrentine A, et al. Impaired regulation of the TNF-alpha converting enzyme/tissue inhibitor of metalloproteinase 3 proteolytic system in skeletal muscle of obese type 2 diabetic patients: a new mechanism of insulin resistance in humans. Diabetologia. 2009;52:2169-81 pubmed publisher
    ..The regulation of TNF-alpha converting enzyme (TACE) and its inhibitor, tissue inhibitor of metalloproteinase 3 (TIMP3), in human type 2 diabetes is unknown...
  16. Johnson J, Sala Newby G, Ismail Y, Aguilera C, Newby A. Low tissue inhibitor of metalloproteinases 3 and high matrix metalloproteinase 14 levels defines a subpopulation of highly invasive foam-cell macrophages. Arterioscler Thromb Vasc Biol. 2008;28:1647-53 pubmed publisher
    ..These cells are highly invasive and have increased proliferation and apoptosis, all properties expected to destabilise atherosclerotic plaques...
  17. Chetty C, Lakka S, Bhoopathi P, Kunigal S, Geiss R, Rao J. Tissue inhibitor of metalloproteinase 3 suppresses tumor angiogenesis in matrix metalloproteinase 2-down-regulated lung cancer. Cancer Res. 2008;68:4736-45 pubmed publisher
    ..These experiments provide the first evidence that inhibition of p-AKT and induction of p-ERK1/2 are crucial events in the induction of TIMP-3-mediated endothelial apoptosis in MMP-2 inhibited lung tumors. ..
  18. Bond M, Murphy G, Bennett M, Amour A, Knauper V, Newby A, et al. Localization of the death domain of tissue inhibitor of metalloproteinase-3 to the N terminus. Metalloproteinase inhibition is associated with proapoptotic activity. J Biol Chem. 2000;275:41358-63 pubmed
  19. Loechel F, Fox J, Murphy G, Albrechtsen R, Wewer U. ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3. Biochem Biophys Res Commun. 2000;278:511-5 pubmed
    ..Cleavage of both IGFBP-3 and -5 by ADAM 12-S was inhibited by TIMP-3, raising the possibility that TIMP-3 is a physiological inhibitor of ADAM 12-S. ..
  20. Kashiwagi M, Tortorella M, Nagase H, Brew K. TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2 (ADAM-TS5). J Biol Chem. 2001;276:12501-4 pubmed
    ..This provides a starting point for developing a biologically available aggrecanase inhibitor suitable for the treatment of arthritis. ..
  21. Hashimoto G, Aoki T, Nakamura H, Tanzawa K, Okada Y. Inhibition of ADAMTS4 (aggrecanase-1) by tissue inhibitors of metalloproteinases (TIMP-1, 2, 3 and 4). FEBS Lett. 2001;494:192-5 pubmed
    ..These results suggest that TIMP-3 is a potent inhibitor against the aggrecanase activity of ADAMTS4 in vivo. ..
  22. Ahonen M, Ala aho R, Baker A, George S, Grenman R, Saarialho Kere U, et al. Antitumor activity and bystander effect of adenovirally delivered tissue inhibitor of metalloproteinases-3. Mol Ther. 2002;5:705-15 pubmed
  23. Wei S, Kashiwagi M, Kota S, Xie Z, Nagase H, Brew K. Reactive site mutations in tissue inhibitor of metalloproteinase-3 disrupt inhibition of matrix metalloproteinases but not tumor necrosis factor-alpha-converting enzyme. J Biol Chem. 2005;280:32877-82 pubmed
  24. Hui W, Barksby H, Young D, Cawston T, McKie N, Rowan A. Oncostatin M in combination with tumour necrosis factor {alpha} induces a chondrocyte membrane associated aggrecanase that is distinct from ADAMTS aggrecanase-1 or -2. Ann Rheum Dis. 2005;64:1624-32 pubmed
    ..Induced membrane associated aggrecanase activity is distinct from known soluble ADAMTS aggrecanases and merits further investigation. ..
  25. Barbazetto I, Hayashi M, Klais C, Yannuzzi L, Allikmets R. A novel TIMP3 mutation associated with Sorsby fundus dystrophy. Arch Ophthalmol. 2005;123:542-3 pubmed
  26. Song B, Wang C, Liu J, Wang X, Lv L, Wei L, et al. MicroRNA-21 regulates breast cancer invasion partly by targeting tissue inhibitor of metalloproteinase 3 expression. J Exp Clin Cancer Res. 2010;29:29 pubmed publisher
    ..in multiple aspects of carcinogenesis, impacts breast cancer invasion by regulating the tissue inhibitor of metalloproteinase 3 (TIMP3) gene...
  27. Feng H, Cheung A, Xue W, Wang Y, Wang X, Fu S, et al. Down-regulation and promoter methylation of tissue inhibitor of metalloproteinase 3 in choriocarcinoma. Gynecol Oncol. 2004;94:375-82 pubmed
    ..expression in neoplastic and normal trophoblastic cells and evaluate the effect of methylation on tissue inhibitor of metalloproteinase 3 (TIMP3) expression in choriocarcinoma (CCA) cells. The Atlas Human Cancer 1...
  28. Wild A, Ramaswamy A, Langer P, Celik I, Fendrich V, Chaloupka B, et al. Frequent methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene in pancreatic endocrine tumors. J Clin Endocrinol Metab. 2003;88:1367-73 pubmed
    ..02). These data suggest a possibly important role of TIMP-3 in the tumorigenesis of human PETs, especially in the development of metastases, which has to be further evaluated in large-scale studies. ..
  29. Lafleur M, Forsyth P, Atkinson S, Murphy G, Edwards D. Perivascular cells regulate endothelial membrane type-1 matrix metalloproteinase activity. Biochem Biophys Res Commun. 2001;282:463-73 pubmed
    ..This interplay may be important for maintenance of blood vessel architecture and neovascularisation. ..
  30. Leco K, Waterhouse P, Sanchez O, Gowing K, Poole A, Wakeham A, et al. Spontaneous air space enlargement in the lungs of mice lacking tissue inhibitor of metalloproteinases-3 (TIMP-3). J Clin Invest. 2001;108:817-29 pubmed
    ..We propose that the deletion of TIMP-3 results in a shift of the TIMP/MMP balance in the lung to favor ECM degradation, culminating in incapacitating illness and a shorter life span. ..
  31. Nothnick W, Zhang X, Zhou H. Steroidal regulation of uterine edema and tissue inhibitors of metalloproteinase (TIMP)-3 messenger RNA expression is altered in TIMP-1-deficient mice. Biol Reprod. 2004;70:500-8 pubmed
    ..These observations suggest that steroids induce uterine TIMP-1 expression and, in turn, that TIMP-1 influences TIMP-3 mRNA expression and uterine edema. ..
  32. Soboleva G, Geis B, Schrewe H, Weber B. Sorsby fundus dystrophy mutation Timp3(S156C) affects the morphological and biochemical phenotype but not metalloproteinase homeostasis. J Cell Physiol. 2003;197:149-56 pubmed
    ..We therefore hypothesize that SFD pathogenesis is due to a loss-of-function mutation in TIMP3. ..
  33. Langton K, McKie N, Smith B, Brown N, Barker M. Sorsby's fundus dystrophy mutations impair turnover of TIMP-3 by retinal pigment epithelial cells. Hum Mol Genet. 2005;14:3579-86 pubmed
    ..These data show that increased deposition of active TIMP-3, rather than dysregulation of metalloproteinase inhibition, is likely to be the primary, initiating event in SFD. ..
  34. Kotzsch M, Farthmann J, Meye A, Fuessel S, Baretton G, Tjan Heijnen V, et al. Prognostic relevance of uPAR-del4/5 and TIMP-3 mRNA expression levels in breast cancer. Eur J Cancer. 2005;41:2760-8 pubmed
    ..Therefore, considering the prognostic impact of two proteolytic factors stemming from complementary protease systems may improve the prediction of disease recurrence in breast cancer. ..
  35. Spurbeck W, Ng C, Strom T, Vanin E, Davidoff A. Enforced expression of tissue inhibitor of matrix metalloproteinase-3 affects functional capillary morphogenesis and inhibits tumor growth in a murine tumor model. Blood. 2002;100:3361-8 pubmed
  36. Yeow K, Kishnani N, Hutton M, Hawkes S, Murphy G, Edwards D. Sorsby's fundus dystrophy tissue inhibitor of metalloproteinases-3 (TIMP-3) mutants have unimpaired matrix metalloproteinase inhibitory activities, but affect cell adhesion to the extracellular matrix. Matrix Biol. 2002;21:75-88 pubmed
  37. Barth J, Yu Y, Song W, Lu K, Dashti A, Huang Y, et al. Oxidised, glycated LDL selectively influences tissue inhibitor of metalloproteinase-3 gene expression and protein production in human retinal capillary pericytes. Diabetologia. 2007;50:2200-8 pubmed
    ..Among the genes encoding for MMPs and TIMPs expressed in retinal pericytes, TIMP3 is uniquely regulated by HOG-LDL. Reduced TIMP3 expression might contribute to microvascular abnormalities in diabetic retinopathy. ..
  38. Gendron C, Kashiwagi M, Hughes C, Caterson B, Nagase H. TIMP-3 inhibits aggrecanase-mediated glycosaminoglycan release from cartilage explants stimulated by catabolic factors. FEBS Lett. 2003;555:431-6 pubmed
    ..Little apoptosis of primary porcine chondrocytes is observed at an effective concentration of N-TIMP-3. These results suggest that TIMP-3 may be a candidate agent for use against cartilage degradation. ..
  39. Selaru F, Olaru A, Kan T, David S, Cheng Y, Mori Y, et al. MicroRNA-21 is overexpressed in human cholangiocarcinoma and regulates programmed cell death 4 and tissue inhibitor of metalloproteinase 3. Hepatology. 2009;49:1595-601 pubmed publisher
    ..MiR-21 is overexpressed in human CCAs. Furthermore, miR-21 may be oncogenic, at least in part, by inhibiting PDCD4 and TIMP3. Finally, these data suggest that TIMP3 is a candidate tumor suppressor gene in the biliary tree. ..
  40. Menghini R, Menini S, Amoruso R, Fiorentino L, Casagrande V, Marzano V, et al. Tissue inhibitor of metalloproteinase 3 deficiency causes hepatic steatosis and adipose tissue inflammation in mice. Gastroenterology. 2009;136:663-72.e4 pubmed publisher
    ..Decreased expression of tissue inhibitor of metalloproteinase 3 (Timp3) is a catalyst for insulin resistance and inflammation...
  41. Wisniewska M, Goettig P, Maskos K, Belouski E, Winters D, Hecht R, et al. Structural determinants of the ADAM inhibition by TIMP-3: crystal structure of the TACE-N-TIMP-3 complex. J Mol Biol. 2008;381:1307-19 pubmed publisher
    ..The combination of favourable functional epitopes together with a considerable flexibility renders TIMP-3 an efficient TACE inhibitor. This structure might provide means to design more efficient TIMP inhibitors of TACE. ..
  42. Lin R, Blumenkranz M, Binkley J, Wu K, Vollrath D. A novel His158Arg mutation in TIMP3 causes a late-onset form of Sorsby fundus dystrophy. Am J Ophthalmol. 2006;142:839-48 pubmed
    ..His158Arg is the first reported TIMP3 SFD coding sequence mutation that does not create an unpaired cysteine. Further study of this unusual mutation may provide insight into the mechanism of SFD pathogenesis. ..
  43. Qi J, Ebrahem Q, Yeow K, Edwards D, Fox P, Anand Apte B. Expression of Sorsby's fundus dystrophy mutations in human retinal pigment epithelial cells reduces matrix metalloproteinase inhibition and may promote angiogenesis. J Biol Chem. 2002;277:13394-400 pubmed
    ..These results also suggest the potential therapeutic use of TIMP-3 or synthetic MMP inhibitors in this disease. ..
  44. Qi J, Ebrahem Q, Moore N, Murphy G, Claesson Welsh L, Bond M, et al. A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med. 2003;9:407-15 pubmed
    ..This property seems to be independent of its MMP-inhibitory activity, indicating a new function for this molecule. ..
  45. Span P, Lindberg R, Manders P, Tjan Heijnen V, Heuvel J, Beex L, et al. Tissue inhibitors of metalloproteinase expression in human breast cancer: TIMP-3 is associated with adjuvant endocrine therapy success. J Pathol. 2004;202:395-402 pubmed
    ..0003). Thus, high tumour levels of the matrix metalloproteinases inhibitor and pro-apoptotic factor TIMP-3 are associated with successful tamoxifen treatment of patients with breast cancer. ..
  46. Darnton S, Hardie L, Muc R, Wild C, Casson A. Tissue inhibitor of metalloproteinase-3 (TIMP-3) gene is methylated in the development of esophageal adenocarcinoma: loss of expression correlates with poor prognosis. Int J Cancer. 2005;115:351-8 pubmed
    ..These studies have demonstrated association between methylation of the TIMP-3 gene and BE and EADC. Reduced expression of TIMP-3 protein in EADC is associated with increased tumour invasiveness and reduced patient survival. ..
  47. Langton K, McKie N, Curtis A, Goodship J, Bond P, Barker M, et al. A novel tissue inhibitor of metalloproteinases-3 mutation reveals a common molecular phenotype in Sorsby's fundus dystrophy. J Biol Chem. 2000;275:27027-31 pubmed
    ..We hypothesize that overexpression of TIMP-3 may prove to be a critical step in the progression of a variety of degenerative retinopathies. ..
  48. Anand Apte B, Bao L, Smith R, Iwata K, Olsen B, Zetter B, et al. A review of tissue inhibitor of metalloproteinases-3 (TIMP-3) and experimental analysis of its effect on primary tumor growth. Biochem Cell Biol. 1996;74:853-62 pubmed
    ..Because recombinant TIMP-3 inhibits endothelial cell migration and tube formation in response to angiogenic factors, we believe that the effect of TIMP-3 on tumor growth seen in this study may be a consequence of its angiostatic action. ..
  49. Alexander C, Hansell E, Behrendtsen O, Flannery M, Kishnani N, Hawkes S, et al. Expression and function of matrix metalloproteinases and their inhibitors at the maternal-embryonic boundary during mouse embryo implantation. Development. 1996;122:1723-36 pubmed
    ..We conclude that administration of MMP inhibitors retards decidual remodeling and growth, and we suggest that the MMPs expressed in precursor stromal cells promote their differentiation and expansion. ..
  50. Felbor U, Stohr H, Amann T, Schonherr U, Weber B. A novel Ser156Cys mutation in the tissue inhibitor of metalloproteinases-3 (TIMP3) in Sorsby's fundus dystrophy with unusual clinical features. Hum Mol Genet. 1995;4:2415-6 pubmed
  51. Wick M, Burger C, Brüsselbach S, Lucibello F, Muller R. A novel member of human tissue inhibitor of metalloproteinases (TIMP) gene family is regulated during G1 progression, mitogenic stimulation, differentiation, and senescence. J Biol Chem. 1994;269:18953-60 pubmed
  52. Apte S, Hayashi K, Seldin M, Mattei M, Hayashi M, Olsen B. Gene encoding a novel murine tissue inhibitor of metalloproteinases (TIMP), TIMP-3, is expressed in developing mouse epithelia, cartilage, and muscle, and is located on mouse chromosome 10. Dev Dyn. 1994;200:177-97 pubmed
    ..We propose a role for TIMP-3 in musculoskeletal and cardiac development, in the morphogenesis of certain epithelial structures, and placental implantation. ..
  53. Weber B, Vogt G, Pruett R, Stohr H, Felbor U. Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy. Nat Genet. 1994;8:352-6 pubmed
    ..We have now identified point mutations in the TIMP3 gene in affected members of two SFD pedigrees. These mutations are predicted to disrupt the tertiary structure and thus the functional properties of the mature protein. ..