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Glypican-3–Deficient Mice Exhibit Developmental Overgrowth and Some of the Abnormalities Typical of Simpson-Golabi-Behmel Syndrome

Glypicans are a family of heparan sulfate proteoglycans that are linked to the cell surface through a glycosyl–phosphatidylinositol anchor. One member of this family, glypican-3 (Gpc3), is mutated in patients with the Simpson-Golabi-Behmel syndrome (SGBS). These patients display pre- and postnatal o...

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Autores principales: Cano-Gauci, Danielle F., Song, Howard H., Yang, Huiling, McKerlie, Colin, Choo, Barbara, Shi, Wen, Pullano, Rose, Piscione, Tino D., Grisaru, Silviu, Soon, Shawn, Sedlackova, Larisa, Tanswell, A. Keith, Mak, Tak W., Yeger, Herman, Lockwood, Gina A., Rosenblum, Norman D., Filmus, Jorge
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199732/
https://www.ncbi.nlm.nih.gov/pubmed/10402475
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author Cano-Gauci, Danielle F.
Song, Howard H.
Yang, Huiling
McKerlie, Colin
Choo, Barbara
Shi, Wen
Pullano, Rose
Piscione, Tino D.
Grisaru, Silviu
Soon, Shawn
Sedlackova, Larisa
Tanswell, A. Keith
Mak, Tak W.
Yeger, Herman
Lockwood, Gina A.
Rosenblum, Norman D.
Filmus, Jorge
author_facet Cano-Gauci, Danielle F.
Song, Howard H.
Yang, Huiling
McKerlie, Colin
Choo, Barbara
Shi, Wen
Pullano, Rose
Piscione, Tino D.
Grisaru, Silviu
Soon, Shawn
Sedlackova, Larisa
Tanswell, A. Keith
Mak, Tak W.
Yeger, Herman
Lockwood, Gina A.
Rosenblum, Norman D.
Filmus, Jorge
author_sort Cano-Gauci, Danielle F.
collection PubMed
description Glypicans are a family of heparan sulfate proteoglycans that are linked to the cell surface through a glycosyl–phosphatidylinositol anchor. One member of this family, glypican-3 (Gpc3), is mutated in patients with the Simpson-Golabi-Behmel syndrome (SGBS). These patients display pre- and postnatal overgrowth, and a varying range of dysmorphisms. The clinical features of SGBS are very similar to the more extensively studied Beckwith-Wiedemann syndrome (BWS). Since BWS has been associated with biallelic expression of insulin-like growth factor II (IGF-II), it has been proposed that GPC3 is a negative regulator of IGF-II. However, there is still no biochemical evidence indicating that GPC3 plays such a role. Here, we report that GPC3-deficient mice exhibit several of the clinical features observed in SGBS patients, including developmental overgrowth, perinatal death, cystic and dyplastic kidneys, and abnormal lung development. A proportion of the mutant mice also display mandibular hypoplasia and an imperforate vagina. In the particular case of the kidney, we demonstrate that there is an early and persistent developmental abnormality of the ureteric bud/collecting system due to increased proliferation of cells in this tissue element. The degree of developmental overgrowth of the GPC3-deficient mice is similar to that of mice deficient in IGF receptor type 2 (IGF2R), a well characterized negative regulator of IGF-II. Unlike the IGF2R-deficient mice, however, the levels of IGF-II in GPC3 knockouts are similar to those of the normal littermates.
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spelling pubmed-21997322008-05-01 Glypican-3–Deficient Mice Exhibit Developmental Overgrowth and Some of the Abnormalities Typical of Simpson-Golabi-Behmel Syndrome Cano-Gauci, Danielle F. Song, Howard H. Yang, Huiling McKerlie, Colin Choo, Barbara Shi, Wen Pullano, Rose Piscione, Tino D. Grisaru, Silviu Soon, Shawn Sedlackova, Larisa Tanswell, A. Keith Mak, Tak W. Yeger, Herman Lockwood, Gina A. Rosenblum, Norman D. Filmus, Jorge J Cell Biol Original Article Glypicans are a family of heparan sulfate proteoglycans that are linked to the cell surface through a glycosyl–phosphatidylinositol anchor. One member of this family, glypican-3 (Gpc3), is mutated in patients with the Simpson-Golabi-Behmel syndrome (SGBS). These patients display pre- and postnatal overgrowth, and a varying range of dysmorphisms. The clinical features of SGBS are very similar to the more extensively studied Beckwith-Wiedemann syndrome (BWS). Since BWS has been associated with biallelic expression of insulin-like growth factor II (IGF-II), it has been proposed that GPC3 is a negative regulator of IGF-II. However, there is still no biochemical evidence indicating that GPC3 plays such a role. Here, we report that GPC3-deficient mice exhibit several of the clinical features observed in SGBS patients, including developmental overgrowth, perinatal death, cystic and dyplastic kidneys, and abnormal lung development. A proportion of the mutant mice also display mandibular hypoplasia and an imperforate vagina. In the particular case of the kidney, we demonstrate that there is an early and persistent developmental abnormality of the ureteric bud/collecting system due to increased proliferation of cells in this tissue element. The degree of developmental overgrowth of the GPC3-deficient mice is similar to that of mice deficient in IGF receptor type 2 (IGF2R), a well characterized negative regulator of IGF-II. Unlike the IGF2R-deficient mice, however, the levels of IGF-II in GPC3 knockouts are similar to those of the normal littermates. The Rockefeller University Press 1999-07-12 /pmc/articles/PMC2199732/ /pubmed/10402475 Text en © 1999 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Cano-Gauci, Danielle F.
Song, Howard H.
Yang, Huiling
McKerlie, Colin
Choo, Barbara
Shi, Wen
Pullano, Rose
Piscione, Tino D.
Grisaru, Silviu
Soon, Shawn
Sedlackova, Larisa
Tanswell, A. Keith
Mak, Tak W.
Yeger, Herman
Lockwood, Gina A.
Rosenblum, Norman D.
Filmus, Jorge
Glypican-3–Deficient Mice Exhibit Developmental Overgrowth and Some of the Abnormalities Typical of Simpson-Golabi-Behmel Syndrome
title Glypican-3–Deficient Mice Exhibit Developmental Overgrowth and Some of the Abnormalities Typical of Simpson-Golabi-Behmel Syndrome
title_full Glypican-3–Deficient Mice Exhibit Developmental Overgrowth and Some of the Abnormalities Typical of Simpson-Golabi-Behmel Syndrome
title_fullStr Glypican-3–Deficient Mice Exhibit Developmental Overgrowth and Some of the Abnormalities Typical of Simpson-Golabi-Behmel Syndrome
title_full_unstemmed Glypican-3–Deficient Mice Exhibit Developmental Overgrowth and Some of the Abnormalities Typical of Simpson-Golabi-Behmel Syndrome
title_short Glypican-3–Deficient Mice Exhibit Developmental Overgrowth and Some of the Abnormalities Typical of Simpson-Golabi-Behmel Syndrome
title_sort glypican-3–deficient mice exhibit developmental overgrowth and some of the abnormalities typical of simpson-golabi-behmel syndrome
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199732/
https://www.ncbi.nlm.nih.gov/pubmed/10402475
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