{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:07:15Z","timestamp":1781107635856,"version":"3.54.1"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,6,6]]},"abstract":"<jats:p>\n                    Insulin-like growth factors (IGFs) I and II are important regulators of cell proliferation and differentiation. After birth, plasma IGFs, representing mostly liver-derived IGFs, circulate in ternary complexes of 150 kDa consisting of one molecule each of IGF, IGF-binding protein (IGFBP) 3, and an acid labile subunit (ALS). Onset of ALS synthesis after birth is the primary factor driving the formation of ternary complexes. Capture of IGFs by ALS is thought to allow the development of a plasma reservoir without negative effects such as hypoglycemia and cell proliferation. To evaluate the importance of ALS and ternary complexes, we have created mice in which the\n                    <jats:italic>ALS<\/jats:italic>\n                    gene has been inactivated. The mutation was inherited in a Mendelian manner, without any effects on survival rates and birth weights. A growth deficit was observed in null mice after 3 weeks of life and reached 13% by 10 weeks. This modest phenotype was observed despite reductions of 62 and 88% in the concentrations of plasma IGF-I and IGFBP-3, respectively. Increased turnover accounted for these reductions because indices of synthesis in liver and kidney were not decreased. Surprisingly, absence of ALS did not affect glucose and insulin homeostasis. Therefore, ALS is required for postnatal accumulation of IGF-I and IGFBP-3 but, consistent with findings supporting a predominant role for locally produced IGF-I, is not critical for growth. This model should be useful to determine whether presence of ALS is needed for other actions of liver-derived IGF-I and for maintenance of homeostasis in presence of high circulating levels of IGF-II.\n                  <\/jats:p>","DOI":"10.1073\/pnas.120172697","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:32:33Z","timestamp":1027679553000},"page":"6868-6873","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":118,"title":["Inactivation of the acid labile subunit gene in mice results in mild retardation of postnatal growth despite profound disruptions in the circulating insulin-like growth factor system"],"prefix":"10.1073","volume":"97","author":[{"given":"Iori","family":"Ueki","sequence":"first","affiliation":[{"name":"Department of Animal Science, Cornell University, Ithaca, NY 14853; Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia; Department of Medicine, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria 3084, Australia; and Department of Biochemistry, McGill University, Montreal, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guck T.","family":"Ooi","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Cornell University, Ithaca, NY 14853; Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia; Department of Medicine, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria 3084, Australia; and Department of Biochemistry, McGill University, Montreal, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel L.","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Cornell University, Ithaca, NY 14853; Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia; Department of Medicine, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria 3084, Australia; and Department of Biochemistry, McGill University, Montreal, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelley R.","family":"Hurst","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Cornell University, Ithaca, NY 14853; Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia; Department of Medicine, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria 3084, Australia; and Department of Biochemistry, McGill University, Montreal, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon A.","family":"Bach","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Cornell University, Ithaca, NY 14853; Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia; Department of Medicine, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria 3084, Australia; and Department of Biochemistry, McGill University, Montreal, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves R.","family":"Boisclair","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Cornell University, Ithaca, NY 14853; Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia; Department of Medicine, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria 3084, Australia; and Department of Biochemistry, McGill University, Montreal, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,5,23]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1996.76.4.1005"},{"key":"e_1_3_3_2_2","first-page":"3","volume":"16","author":"Jones J I","year":"1995","unstructured":"J I Jones, 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