{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:16:49Z","timestamp":1790522209705,"version":"4.1.0"},"reference-count":45,"publisher":"Cold Spring Harbor Laboratory","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[1990,7]]},"abstract":"<jats:p>We determined the expression pattern of the tissue inhibitor of metalloproteinase (TIMP) in the development of the mouse embryo using in situ hybridization and transgenesis. Localized TIMP RNA was first detected at 13.5 days post conceptus (p.c.) in tissues undergoing osteogenesis, such as the mandible, ribs, and calvaria. As development proceeded, TIMP RNA could be detected at additional sites, including the tooth buds, vertebrae, and long bones. To define the sequences regulating TIMP expression, we generated transgenic mice that expressed the Escherichia coli beta-galactosidase gene under control of a 5' region of the mouse TIMP gene containing -2158 to -58 bp upstream of the initiator ATG. By use of an in situ assay for beta-galactosidase activity, the TIMP-lacZ fusion gene product was localized to tissues that also expressed the endogenous TIMP gene, such as the mandible, calvaria, and vertebrae. The localization of TIMP to regions of intramembranous and endochondral bone is similar to that previously reported for TGF-beta, a growth modulator believed to be involved in regulation of extracellular matrix (ECM) formation. Thus, the expression of TIMP in these regions is consistent with it playing a role in ECM deposition and turnover in development.<\/jats:p>","DOI":"10.1101\/gad.4.7.1094","type":"journal-article","created":{"date-parts":[[2007,6,5]],"date-time":"2007-06-05T21:15:46Z","timestamp":1181078146000},"page":"1094-1106","source":"Crossref","is-referenced-by-count":62,"title":["Developmental expression of the endogenous TIMP gene and a TIMP-lacZ fusion gene in transgenic mice."],"prefix":"10.1101","volume":"4","author":[{"given":"A M","family":"Flenniken","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B R","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[1990,7,1]]},"reference":[{"key":"2021111320075620000_4.7.1094.1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90611-8"},{"key":"2021111320075620000_4.7.1094.2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/15.3.1019"},{"key":"2021111320075620000_4.7.1094.3","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.107.5.1969"},{"key":"2021111320075620000_4.7.1094.4","doi-asserted-by":"publisher","DOI":"10.1042\/bj1950159"},{"key":"2021111320075620000_4.7.1094.5","doi-asserted-by":"publisher","DOI":"10.1042\/bj2110313"},{"key":"2021111320075620000_4.7.1094.6","doi-asserted-by":"publisher","DOI":"10.1021\/bi00591a005"},{"key":"2021111320075620000_4.7.1094.7","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(85)90358-3"},{"key":"2021111320075620000_4.7.1094.8","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/S0021-9258(19)57322-7","article-title":"In vitro synthesis of the active tissue inhibitor of metalloproteinases encoded by a complementary DNA from virus-infected murine fibroblasts.","volume":"263","year":"1988","journal-title":"J. Biol. Chem."},{"key":"2021111320075620000_4.7.1094.9","first-page":"3227","article-title":"Presence of transcription regulatory elements within an intron of the virus-inducible murine TIMP gene.","volume":"8","year":"1988","journal-title":"Mol. Cell Biol."},{"key":"2021111320075620000_4.7.1094.10","doi-asserted-by":"crossref","unstructured":"Dannenberg, A.M. and M. Suga. 1981. Histochemical stains for macrophages in cell smears and tissue sections: \u03b2-galactosidase, acid phosphatase, nonspecific esterase, succinic dehydrogenase, and cytochrome oxidase. In Methods for studying mononuclear phagocytes (ed. D. Adams, P. Edelson, and M. Koren) pp. 375\u2013396. Academic Press, New York.","DOI":"10.1016\/B978-0-12-044220-1.50047-7"},{"key":"2021111320075620000_4.7.1094.11","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2.3.361"},{"key":"2021111320075620000_4.7.1094.12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114215"},{"key":"2021111320075620000_4.7.1094.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.3175621"},{"key":"2021111320075620000_4.7.1094.14","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1002\/j.1460-2075.1987.tb02449.x","article-title":"Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor.","volume":"6","year":"1987","journal-title":"EMBO J."},{"key":"2021111320075620000_4.7.1094.15","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(83)90418-9"},{"key":"2021111320075620000_4.7.1094.16","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1128\/jvi.62.9.3077-3083.1988","article-title":"Expression of interferoninduced genes in different tissues of mice.","volume":"62","year":"1988","journal-title":"J. Virol."},{"key":"2021111320075620000_4.7.1094.17","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1002\/j.1460-2075.1987.tb04804.x","article-title":"Characterization and expression of a murine gene homologous to human EPA\/TIMP: a virus-induced gene in the mouse.","volume":"6","year":"1987","journal-title":"EMBO J."},{"key":"2021111320075620000_4.7.1094.18","doi-asserted-by":"publisher","DOI":"10.1126\/science.2497519"},{"key":"2021111320075620000_4.7.1094.19","first-page":"101","article-title":"Expression and regulation of E. coli lacZ gene fusions in mammalian cells.","volume":"2","year":"1983","journal-title":"J. Mol. Appl. Genet."},{"key":"2021111320075620000_4.7.1094.20","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0174-173X(84)80015-1","article-title":"Regulation of mammalian collagenase.","volume":"4","year":"1984","journal-title":"Collagen Rel. Res."},{"key":"2021111320075620000_4.7.1094.21","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.105.6.2861"},{"key":"2021111320075620000_4.7.1094.22","unstructured":"Hogan, B., F. Costantini, and E. Lacey. 1986. Introduction of new genetic information into the developing mouse embryo. In Manipulating the mouse embryo. pp. 152\u2013203. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York."},{"key":"2021111320075620000_4.7.1094.23","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.105.1.473"},{"key":"2021111320075620000_4.7.1094.24","doi-asserted-by":"crossref","first-page":"4337","DOI":"10.1016\/S0021-9258(17)35666-1","article-title":"Transforming growth factor-\u03b2 stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix.","volume":"261","year":"1986","journal-title":"J. Biol. Chem."},{"key":"2021111320075620000_4.7.1094.25","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1242\/dev.105.4.707","article-title":"Inducible expression of an hsp6S-lacZ hybrid gene in transgenic mice.","volume":"105","year":"1989","journal-title":"Development"},{"key":"2021111320075620000_4.7.1094.26","unstructured":"Leeson, C.R., T.S. Leeson, and A.A. Paparo. 1985. The digestive system. In Textbook of histology, pp. 317\u2013326. W.B. Saunders Co., Toronto."},{"key":"2021111320075620000_4.7.1094.27","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1242\/dev.104.2.263","article-title":"Embryonic expression pattern of TGF beta type-1 RNA suggests both paracrine and autocrine mechanisms of action.","volume":"104","year":"1988","journal-title":"Development"},{"key":"2021111320075620000_4.7.1094.28","unstructured":"Maniatis, T., E.F. Fritsch, and J. Sambrook. 1982. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York."},{"key":"2021111320075620000_4.7.1094.29","doi-asserted-by":"publisher","DOI":"10.1177\/6.1.22"},{"key":"2021111320075620000_4.7.1094.30","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/12.18.7035"},{"key":"2021111320075620000_4.7.1094.31","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90613-6"},{"key":"2021111320075620000_4.7.1094.32","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(88)90078-X"},{"key":"2021111320075620000_4.7.1094.33","first-page":"55","article-title":"Current views of collagen\ndegradation.","volume":"2","year":"1985","journal-title":"BioEssays"},{"key":"2021111320075620000_4.7.1094.34","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1016\/S0021-9258(18)89475-3","article-title":"Biosynthesis of\ntissue inhibitor of metalloproteinases by human fibroblasts\nin culture.","volume":"260","year":"1985","journal-title":"J. Biol. Chem."},{"key":"2021111320075620000_4.7.1094.35","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1242\/dev.105.3.575","article-title":"Developmental expression of tissue inhibitor\nof metalloproteinase (TIMP) RNA.","volume":"105","year":"1989","journal-title":"Development"},{"key":"2021111320075620000_4.7.1094.36","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1016\/S0021-9258(18)94267-5","article-title":"Independent regulation of collagenase, 72-kDa progelantinase, and metalloendoproteinase inhibitor expression in human fibroblasts\nby transforming growth factor-\u03b2.","volume":"264","year":"1989","journal-title":"J. Biol. Chem."},{"key":"2021111320075620000_4.7.1094.37","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1242\/dev.106.4.759","article-title":"Expression of transforming growth factor \u03b22 RNA during\nmurine embryogenesis.","volume":"106","year":"1989","journal-title":"Development"},{"key":"2021111320075620000_4.7.1094.38","unstructured":"Rugh, R. 1968. The mouse: its reproduction and development. Burgess Publishing Co., Minneapolis."},{"key":"2021111320075620000_4.7.1094.39","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/0304-4165(86)90292-8","article-title":"Hormonal control of collagenase inhibitor production in rabbit uterine\ncervical fibroblast-like cells.","volume":"883","year":"1986","journal-title":"Biochim. Biophys. Acta"},{"key":"2021111320075620000_4.7.1094.40","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1242\/dev.102.3.461","article-title":"Enhanced expression of TGF-\u03b2 and c-fos mRNAs in the growth plates of developing human long bones.","volume":"102","year":"1988","journal-title":"Development"},{"key":"2021111320075620000_4.7.1094.41","doi-asserted-by":"crossref","unstructured":"Southern, E. 1975. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol. 98: 5035-17.","DOI":"10.1016\/S0022-2836(75)80083-0"},{"key":"2021111320075620000_4.7.1094.42","first-page":"191","article-title":"Proteolytic degradation of extracellular matrix in tumour invasion.","volume":"907","year":"1987","journal-title":"Biochim. Biophys. Acta"},{"key":"2021111320075620000_4.7.1094.43","doi-asserted-by":"crossref","first-page":"12259","DOI":"10.1016\/S0021-9258(17)44167-6","article-title":"Human skin fibroblast collagenase inhibitor.","volume":"258","year":"1983","journal-title":"J. Biol. Chem."},{"key":"2021111320075620000_4.7.1094.44","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0174-173X(85)80038-8","article-title":"Human skin fibroblast collagenase: interaction with\nsubstrate and inhibitor.","volume":"5","year":"1985","journal-title":"Collagen Rel. Res."},{"key":"2021111320075620000_4.7.1094.45","doi-asserted-by":"publisher","DOI":"10.1007\/BF00291161"}],"container-title":["Genes &amp; Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/gad.4.7.1094","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T04:09:03Z","timestamp":1636862943000},"score":1,"resource":{"primary":{"URL":"http:\/\/genesdev.cshlp.org\/lookup\/doi\/10.1101\/gad.4.7.1094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,7]]},"references-count":45,"journal-issue":{"issue":"7","published-print":{"date-parts":[[1990,7]]}},"alternative-id":["10.1101\/gad.4.7.1094"],"URL":"https:\/\/doi.org\/10.1101\/gad.4.7.1094","relation":{},"ISSN":["0890-9369","1549-5477"],"issn-type":[{"value":"0890-9369","type":"print"},{"value":"1549-5477","type":"electronic"}],"subject":[],"published":{"date-parts":[[1990,7]]}}}