{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T18:13:11Z","timestamp":1697911991539},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,5,23]],"date-time":"2005-05-23T00:00:00Z","timestamp":1116806400000},"content-version":"vor","delay-in-days":7416,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[1985,2]]},"abstract":"Abstract<\/jats:title>The induction of polydactyly in mouse embryos heterozygous for Hemimelia\u2010extra toe (Hm<\/jats:italic>x<\/jats:sup>) is associated with aberrant outgrowth of the developing autopod on day 12 of gestation. We have quantitated the rate of DNA synthesis and the activity of cAMP\u2010phosphodiesterase (PDE) that is characteristic of the prospective polydactylous region. Mid\u2010stage 18 hind\u2010limb buds were labeled with [3<\/jats:sup>H]dThd either in situ using whole embryo culture, or as isolated preaxial autopod fragments cultured on a membrane substratum. The mean specific activities of incorporation were compared for normal (+\/+) and mutant (Hm<\/jats:italic>x<\/jats:sup>\/+) genotypes. A significant (P \u2264 0.01) 19% increase, peculiar to the prospective polydactylous region, was measured after 4 hours in embryo culture. The same increment was detected after 4 hours in organ culture, but was amplified linearly to 55% when incubation was extended to 20 hours. During this period, continuous exposure to 1.0 mM IBMX (3\u2010isobutyl\u20101\u2010methyl xanthine), an inhibitor of cAMP\u2010PDE activity, \u201cslowed down\u201d the rate of DNA synthesis to untreated +\/+ proportions. When cAMP\u2010PDE activity was assayed in uncultured autopods, a significant (P \u2264 0.01) 18% increase was detected within the prospective polydactylous region specifically on stage 18 of gestation. This is the developmental phase during which polydactylous outgrowth is induced in situ. Thus, uncontrolled cAMP\u2010PDE activity may, in part, provoke the enhanced rate of cell proliferation.<\/jats:p>","DOI":"10.1002\/tera.1420310116","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T13:11:39Z","timestamp":1118495499000},"page":"155-166","source":"Crossref","is-referenced-by-count":6,"title":["Elevated rate of DNA synthesis and its correlation to cAMP\u2010phosphodiesterase activity during induction of polydactyly in mouse embryos heterozygous for Hemimelia\u2010extra toe (Hm<\/i>x<\/sup>)"],"prefix":"10.1002","volume":"31","author":[{"given":"Thomas B.","family":"Knudsen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William A.","family":"Elmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devendra M.","family":"Kochhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,5,23]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(72)90460-5"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(77)90160-9"},{"key":"e_1_2_1_4_1","first-page":"193","article-title":"The role of cyclic AMP in cell proliferation: A critical assessment of the evidence","volume":"15","author":"Boynton A. 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