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 |
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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 |
format | Article |
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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.</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. 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.</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 ; Wu, Minyao ; Mohan, Subburaman ; Föll, Jürgen ; Wanke, Rüdiger ; Froehlich, Thomas ; Arnold, Georg J ; Lahm, Harald ; Kolb, Helmut J ; Wolf, Eckhard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3769-e6c914b066ace935a1d564f5db90f5ab3e3c875607331f99e67b919e8c560d9c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adipose tissue</topic><topic>Bioavailability</topic><topic>Body weight</topic><topic>Body weight gain</topic><topic>Cardiac muscle</topic><topic>Cell proliferation</topic><topic>Cytomegalovirus</topic><topic>Gene expression</topic><topic>Genotypes</topic><topic>Glucose</topic><topic>Growth factors</topic><topic>In vivo methods and tests</topic><topic>Insulin</topic><topic>Insulin-like growth factor I</topic><topic>Insulin-like growth factor II</topic><topic>Insulin-like growth factor-binding protein 2</topic><topic>Insulin-like growth factors</topic><topic>Pancreas</topic><topic>Postpartum period</topic><topic>Proteins</topic><topic>Serum levels</topic><topic>Skeletal muscle</topic><topic>Spleen</topic><topic>Transgenes</topic><topic>Transgenic animals</topic><topic>Transgenic mice</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><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><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hoeflich, Andreas</au><au>Wu, Minyao</au><au>Mohan, Subburaman</au><au>Föll, Jürgen</au><au>Wanke, Rüdiger</au><au>Froehlich, Thomas</au><au>Arnold, Georg J</au><au>Lahm, Harald</au><au>Kolb, Helmut J</au><au>Wolf, Eckhard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of Insulin-Like Growth Factor-Binding Protein-2 in Transgenic Mice Reduces Postnatal Body Weight Gain</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><date>1999-12-01</date><risdate>1999</risdate><volume>140</volume><issue>12</issue><spage>5488</spage><epage>5496</epage><pages>5488-5496</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><abstract>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.</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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