Overexpression of Insulin-Like Growth Factor-Binding Protein-2 in Transgenic Mice Reduces Postnatal Body Weight Gain

Insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) has been shown to inhibit IGF-dependent cell proliferation in a number of in vitro studies. However, no in vivo model of IGFBP-2 overexpression has been established so far. Therefore, we have generated transgenic mice, in which expression...

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Veröffentlicht in:Endocrinology (Philadelphia) 1999-12, Vol.140 (12), p.5488-5496
Hauptverfasser: Hoeflich, Andreas, Wu, Minyao, Mohan, Subburaman, Föll, Jürgen, Wanke, Rüdiger, Froehlich, Thomas, Arnold, Georg J, Lahm, Harald, Kolb, Helmut J, Wolf, Eckhard
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container_end_page 5496
container_issue 12
container_start_page 5488
container_title Endocrinology (Philadelphia)
container_volume 140
creator Hoeflich, Andreas
Wu, Minyao
Mohan, Subburaman
Föll, Jürgen
Wanke, Rüdiger
Froehlich, Thomas
Arnold, Georg J
Lahm, Harald
Kolb, Helmut J
Wolf, Eckhard
description Insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) has been shown to inhibit IGF-dependent cell proliferation in a number of in vitro studies. However, no in vivo model of IGFBP-2 overexpression has been established so far. Therefore, we have generated transgenic mice, in which expression of a mouse IGFBP-2 complementary DNA is controlled by the cytomegalovirus (CMV) promoter. In two independent transgenic strains, transgene expression was highest in pancreas and stomach, followed by skeletal muscle, heart, colon, spleen, adipose tissue, brain, and kidney. Within the pancreas, IGFBP-2 expression was found in the islets but not in the exocrine part. Serum IGFBP-2 levels of CMV-IGFBP-2 transgenic mice were about 3-fold (P < 0.05) increased, compared with controls, whereas serum levels of IGF-I and IGF-II were unaffected by IGFBP-2 overexpression. Fasted serum glucose and fasted insulin levels were slightly reduced in transgenic mice, compared with controls. Postprandial serum glucose insulin levels were not affected by the genotype. At days later than 23, body weights of transgenic mice were significantly (P < 0.05) reduced in both sexes, compared with nontransgenic littermates. This reduction in body weight was mainly attributable to significantly (P < 0.05) lower carcass weights of CMV-IGFBP-2 transgenic vs. control mice. In contrast, absolute organ weights were not (or only as a tendency) reduced, except for the weight of the spleen, which was significantly (P < 0.05) lower in male transgenic than in control mice. Our data suggest that IGFBP-2 represents a negative regulator of postnatal growth in mice, potentially by reducing the bioavailability of IGF-I.
doi_str_mv 10.1210/endo.140.12.7169
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However, no in vivo model of IGFBP-2 overexpression has been established so far. Therefore, we have generated transgenic mice, in which expression of a mouse IGFBP-2 complementary DNA is controlled by the cytomegalovirus (CMV) promoter. In two independent transgenic strains, transgene expression was highest in pancreas and stomach, followed by skeletal muscle, heart, colon, spleen, adipose tissue, brain, and kidney. Within the pancreas, IGFBP-2 expression was found in the islets but not in the exocrine part. Serum IGFBP-2 levels of CMV-IGFBP-2 transgenic mice were about 3-fold (P &lt; 0.05) increased, compared with controls, whereas serum levels of IGF-I and IGF-II were unaffected by IGFBP-2 overexpression. Fasted serum glucose and fasted insulin levels were slightly reduced in transgenic mice, compared with controls. Postprandial serum glucose insulin levels were not affected by the genotype. At days later than 23, body weights of transgenic mice were significantly (P &lt; 0.05) reduced in both sexes, compared with nontransgenic littermates. This reduction in body weight was mainly attributable to significantly (P &lt; 0.05) lower carcass weights of CMV-IGFBP-2 transgenic vs. control mice. In contrast, absolute organ weights were not (or only as a tendency) reduced, except for the weight of the spleen, which was significantly (P &lt; 0.05) lower in male transgenic than in control mice. Our data suggest that IGFBP-2 represents a negative regulator of postnatal growth in mice, potentially by reducing the bioavailability of IGF-I.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/endo.140.12.7169</identifier><language>eng</language><publisher>Washington: Endocrine Society</publisher><subject>Adipose tissue ; Bioavailability ; Body weight ; Body weight gain ; Cardiac muscle ; Cell proliferation ; Cytomegalovirus ; Gene expression ; Genotypes ; Glucose ; Growth factors ; In vivo methods and tests ; Insulin ; Insulin-like growth factor I ; Insulin-like growth factor II ; Insulin-like growth factor-binding protein 2 ; Insulin-like growth factors ; Pancreas ; Postpartum period ; Proteins ; Serum levels ; Skeletal muscle ; Spleen ; Transgenes ; Transgenic animals ; Transgenic mice</subject><ispartof>Endocrinology (Philadelphia), 1999-12, Vol.140 (12), p.5488-5496</ispartof><rights>Copyright © 1999 by The Endocrine Society 1999</rights><rights>Copyright © 1999 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3769-e6c914b066ace935a1d564f5db90f5ab3e3c875607331f99e67b919e8c560d9c3</citedby><cites>FETCH-LOGICAL-c3769-e6c914b066ace935a1d564f5db90f5ab3e3c875607331f99e67b919e8c560d9c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Hoeflich, Andreas</creatorcontrib><creatorcontrib>Wu, Minyao</creatorcontrib><creatorcontrib>Mohan, Subburaman</creatorcontrib><creatorcontrib>Föll, Jürgen</creatorcontrib><creatorcontrib>Wanke, Rüdiger</creatorcontrib><creatorcontrib>Froehlich, Thomas</creatorcontrib><creatorcontrib>Arnold, Georg J</creatorcontrib><creatorcontrib>Lahm, Harald</creatorcontrib><creatorcontrib>Kolb, Helmut J</creatorcontrib><creatorcontrib>Wolf, Eckhard</creatorcontrib><title>Overexpression of Insulin-Like Growth Factor-Binding Protein-2 in Transgenic Mice Reduces Postnatal Body Weight Gain</title><title>Endocrinology (Philadelphia)</title><description>Insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) has been shown to inhibit IGF-dependent cell proliferation in a number of in vitro studies. 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At days later than 23, body weights of transgenic mice were significantly (P &lt; 0.05) reduced in both sexes, compared with nontransgenic littermates. This reduction in body weight was mainly attributable to significantly (P &lt; 0.05) lower carcass weights of CMV-IGFBP-2 transgenic vs. control mice. In contrast, absolute organ weights were not (or only as a tendency) reduced, except for the weight of the spleen, which was significantly (P &lt; 0.05) lower in male transgenic than in control mice. Our data suggest that IGFBP-2 represents a negative regulator of postnatal growth in mice, potentially by reducing the bioavailability of IGF-I.</description><subject>Adipose tissue</subject><subject>Bioavailability</subject><subject>Body weight</subject><subject>Body weight gain</subject><subject>Cardiac muscle</subject><subject>Cell proliferation</subject><subject>Cytomegalovirus</subject><subject>Gene expression</subject><subject>Genotypes</subject><subject>Glucose</subject><subject>Growth factors</subject><subject>In vivo methods and tests</subject><subject>Insulin</subject><subject>Insulin-like growth factor I</subject><subject>Insulin-like growth factor II</subject><subject>Insulin-like growth factor-binding protein 2</subject><subject>Insulin-like growth factors</subject><subject>Pancreas</subject><subject>Postpartum period</subject><subject>Proteins</subject><subject>Serum levels</subject><subject>Skeletal muscle</subject><subject>Spleen</subject><subject>Transgenes</subject><subject>Transgenic animals</subject><subject>Transgenic mice</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><recordid>eNqNkEFLwzAYhoMoOKd3jwGP0pk0bbIc3XBzMNmQiceSpl-3zJnMpFX3722t4EnwFN58z_slPAhdUjKgMSU3YAs3oEmbBoJyeYR6VCZpJKggx6hHCGWRiGNxis5C2DYxSRLWQ9XiHTx87j2EYJzFrsQzG-qdsdHcvACeevdRbfBE6cr5aGRsYewaL72roEFibCxeeWXDGqzR-MFowI9Q1BoCXrpQWVWpHR654oCfwaw3FZ4qY8_RSal2AS5-zj56mtytxvfRfDGdjW_nkWaCywi4ljTJCedKg2SpokXKkzItcknKVOUMmB6KlBPBGC2lBC5ySSUMdXNXSM366Krbu_furYZQZVtXe9s8mTHKSEoSRmlDkY7S3oXgocz23rwqf8goyVq3Wes2a9w2KWvdNpXrruLq_X9o0dHtRHtj4Vv372f-bH4BYiyNkw</recordid><startdate>19991201</startdate><enddate>19991201</enddate><creator>Hoeflich, Andreas</creator><creator>Wu, Minyao</creator><creator>Mohan, Subburaman</creator><creator>Föll, Jürgen</creator><creator>Wanke, Rüdiger</creator><creator>Froehlich, Thomas</creator><creator>Arnold, Georg J</creator><creator>Lahm, Harald</creator><creator>Kolb, Helmut J</creator><creator>Wolf, Eckhard</creator><general>Endocrine Society</general><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope></search><sort><creationdate>19991201</creationdate><title>Overexpression of Insulin-Like Growth Factor-Binding Protein-2 in Transgenic Mice Reduces Postnatal Body Weight Gain</title><author>Hoeflich, Andreas ; 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However, no in vivo model of IGFBP-2 overexpression has been established so far. Therefore, we have generated transgenic mice, in which expression of a mouse IGFBP-2 complementary DNA is controlled by the cytomegalovirus (CMV) promoter. In two independent transgenic strains, transgene expression was highest in pancreas and stomach, followed by skeletal muscle, heart, colon, spleen, adipose tissue, brain, and kidney. Within the pancreas, IGFBP-2 expression was found in the islets but not in the exocrine part. Serum IGFBP-2 levels of CMV-IGFBP-2 transgenic mice were about 3-fold (P &lt; 0.05) increased, compared with controls, whereas serum levels of IGF-I and IGF-II were unaffected by IGFBP-2 overexpression. Fasted serum glucose and fasted insulin levels were slightly reduced in transgenic mice, compared with controls. Postprandial serum glucose insulin levels were not affected by the genotype. At days later than 23, body weights of transgenic mice were significantly (P &lt; 0.05) reduced in both sexes, compared with nontransgenic littermates. This reduction in body weight was mainly attributable to significantly (P &lt; 0.05) lower carcass weights of CMV-IGFBP-2 transgenic vs. control mice. In contrast, absolute organ weights were not (or only as a tendency) reduced, except for the weight of the spleen, which was significantly (P &lt; 0.05) lower in male transgenic than in control mice. Our data suggest that IGFBP-2 represents a negative regulator of postnatal growth in mice, potentially by reducing the bioavailability of IGF-I.</abstract><cop>Washington</cop><pub>Endocrine Society</pub><doi>10.1210/endo.140.12.7169</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals
subjects Adipose tissue
Bioavailability
Body weight
Body weight gain
Cardiac muscle
Cell proliferation
Cytomegalovirus
Gene expression
Genotypes
Glucose
Growth factors
In vivo methods and tests
Insulin
Insulin-like growth factor I
Insulin-like growth factor II
Insulin-like growth factor-binding protein 2
Insulin-like growth factors
Pancreas
Postpartum period
Proteins
Serum levels
Skeletal muscle
Spleen
Transgenes
Transgenic animals
Transgenic mice
title Overexpression of Insulin-Like Growth Factor-Binding Protein-2 in Transgenic Mice Reduces Postnatal Body Weight Gain
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