Unbound (bioavailable) IGF1 enhances somatic growth

Autores
Elis, Sebastien; Wu, Yingjie; Courtland, Hayden William; Cannata, Dara; Sun, Hui; Beth On, Mordechay; Liu, Chengyu; Jasper, Hector Guillermo; Domené, Horacio; Karabatas, Liliana Margarita; Guida, Clara; Basta Pljakic, Jelena; Cardoso, Luis; Rosen, Clifford J.; Frystyk, Jan; Yakar, Shoshana
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Understanding insulin-like growth factor-1 (IGF1) biology is of particular importance because, apart from its role in mediating growth, it plays key roles in cellular transformation, organ regeneration, immune function, development of the musculoskeletal system and aging. IGF1 bioactivity is modulated by its binding to IGF-binding proteins (IGFBPs) and the acid labile subunit (ALS), which are present in serum and tissues. To determine whether IGF1 binding to IGFBPs is necessary to facilitate normal growth and development, we used a gene-targeting approach and generated two novel knock-in mouse models of mutated IGF1, in which the native Igf1 gene was replaced by Des-Igf1 (KID mice) or R3-Igf1 (KIR mice). The KID and KIR mutant proteins have reduced affinity for the IGFBPs, and therefore present as unbound IGF1, or ‘free IGF1’. We found that both KID and KIR mice have reduced serum IGF1 levels and a concomitant increase in serum growth hormone levels. Ternary complex formation of IGF1 with the IGFBPs and the ALS was markedly reduced in sera from KID and KIR mice compared with wild type. Both mutant mice showed increased body weight, body and bone lengths, and relative lean mass. We found selective organomegaly of the spleen, kidneys and uterus, enhanced mammary gland complexity, and increased skeletal acquisition. The KID and KIR models show unequivocally that IGF1-complex formation with the IGFBPs is fundamental for establishing normal body and organ size, and that uncontrolled IGF bioactivity could lead to pathological conditions.
Fil: Elis, Sebastien. Mount Sinai School of Medicine; Estados Unidos
Fil: Wu, Yingjie. Mount Sinai School of Medicine; Estados Unidos
Fil: Courtland, Hayden William. Mount Sinai School of Medicine; Estados Unidos
Fil: Cannata, Dara. Mount Sinai School of Medicine; Estados Unidos
Fil: Sun, Hui. Mount Sinai School of Medicine; Estados Unidos
Fil: Beth On, Mordechay. Mount Sinai School of Medicine; Estados Unidos
Fil: Liu, Chengyu. National Institutes of Health; Estados Unidos
Fil: Jasper, Hector Guillermo. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Domené, Horacio. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina
Fil: Karabatas, Liliana Margarita. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Guida, Clara. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina
Fil: Basta Pljakic, Jelena. City University Of New York. The City College Of New York.; Estados Unidos
Fil: Cardoso, Luis. City University Of New York. The City College Of New York.; Estados Unidos
Fil: Rosen, Clifford J.. Maine Medical Center Research Institute; Estados Unidos
Fil: Frystyk, Jan. Aarhus University Hospital; Dinamarca
Fil: Yakar, Shoshana. Mount Sinai School of Medicine; Estados Unidos
Materia
insulin-like growth factor-1 (IGF1)
IGF1 bioactivity
knock-in mouse models of mutated IGF1
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/103584
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/103584
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Unbound (bioavailable) IGF1 enhances somatic growthElis, SebastienWu, YingjieCourtland, Hayden WilliamCannata, DaraSun, HuiBeth On, MordechayLiu, ChengyuJasper, Hector GuillermoDomené, HoracioKarabatas, Liliana MargaritaGuida, ClaraBasta Pljakic, JelenaCardoso, LuisRosen, Clifford J.Frystyk, JanYakar, Shoshanainsulin-like growth factor-1 (IGF1)IGF1 bioactivityknock-in mouse models of mutated IGF1https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Understanding insulin-like growth factor-1 (IGF1) biology is of particular importance because, apart from its role in mediating growth, it plays key roles in cellular transformation, organ regeneration, immune function, development of the musculoskeletal system and aging. IGF1 bioactivity is modulated by its binding to IGF-binding proteins (IGFBPs) and the acid labile subunit (ALS), which are present in serum and tissues. To determine whether IGF1 binding to IGFBPs is necessary to facilitate normal growth and development, we used a gene-targeting approach and generated two novel knock-in mouse models of mutated IGF1, in which the native Igf1 gene was replaced by Des-Igf1 (KID mice) or R3-Igf1 (KIR mice). The KID and KIR mutant proteins have reduced affinity for the IGFBPs, and therefore present as unbound IGF1, or ‘free IGF1’. We found that both KID and KIR mice have reduced serum IGF1 levels and a concomitant increase in serum growth hormone levels. Ternary complex formation of IGF1 with the IGFBPs and the ALS was markedly reduced in sera from KID and KIR mice compared with wild type. Both mutant mice showed increased body weight, body and bone lengths, and relative lean mass. We found selective organomegaly of the spleen, kidneys and uterus, enhanced mammary gland complexity, and increased skeletal acquisition. The KID and KIR models show unequivocally that IGF1-complex formation with the IGFBPs is fundamental for establishing normal body and organ size, and that uncontrolled IGF bioactivity could lead to pathological conditions.Fil: Elis, Sebastien. Mount Sinai School of Medicine; Estados UnidosFil: Wu, Yingjie. Mount Sinai School of Medicine; Estados UnidosFil: Courtland, Hayden William. Mount Sinai School of Medicine; Estados UnidosFil: Cannata, Dara. Mount Sinai School of Medicine; Estados UnidosFil: Sun, Hui. Mount Sinai School of Medicine; Estados UnidosFil: Beth On, Mordechay. Mount Sinai School of Medicine; Estados UnidosFil: Liu, Chengyu. National Institutes of Health; Estados UnidosFil: Jasper, Hector Guillermo. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Domené, Horacio. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; ArgentinaFil: Karabatas, Liliana Margarita. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guida, Clara. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; ArgentinaFil: Basta Pljakic, Jelena. City University Of New York. The City College Of New York.; Estados UnidosFil: Cardoso, Luis. City University Of New York. The City College Of New York.; Estados UnidosFil: Rosen, Clifford J.. Maine Medical Center Research Institute; Estados UnidosFil: Frystyk, Jan. Aarhus University Hospital; DinamarcaFil: Yakar, Shoshana. Mount Sinai School of Medicine; Estados UnidosCompany of Biologists2011-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/103584Elis, Sebastien; Wu, Yingjie; Courtland, Hayden William; Cannata, Dara; Sun, Hui; et al.; Unbound (bioavailable) IGF1 enhances somatic growth; Company of Biologists; Disease Models And Mechanisms; 4; 4-2011; 649-6581754-84031754-8411CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://dmm.biologists.org/cgi/pmidlookup?view=long&pmid=21628395info:eu-repo/semantics/altIdentifier/doi/10.1242/dmm.006775info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:48:43Zoai:ri.conicet.gov.ar:11336/103584instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:48:43.978CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Unbound (bioavailable) IGF1 enhances somatic growth
title Unbound (bioavailable) IGF1 enhances somatic growth
spellingShingle Unbound (bioavailable) IGF1 enhances somatic growth
Elis, Sebastien
insulin-like growth factor-1 (IGF1)
IGF1 bioactivity
knock-in mouse models of mutated IGF1
title_short Unbound (bioavailable) IGF1 enhances somatic growth
title_full Unbound (bioavailable) IGF1 enhances somatic growth
title_fullStr Unbound (bioavailable) IGF1 enhances somatic growth
title_full_unstemmed Unbound (bioavailable) IGF1 enhances somatic growth
title_sort Unbound (bioavailable) IGF1 enhances somatic growth
dc.creator.none.fl_str_mv Elis, Sebastien
Wu, Yingjie
Courtland, Hayden William
Cannata, Dara
Sun, Hui
Beth On, Mordechay
Liu, Chengyu
Jasper, Hector Guillermo
Domené, Horacio
Karabatas, Liliana Margarita
Guida, Clara
Basta Pljakic, Jelena
Cardoso, Luis
Rosen, Clifford J.
Frystyk, Jan
Yakar, Shoshana
author Elis, Sebastien
author_facet Elis, Sebastien
Wu, Yingjie
Courtland, Hayden William
Cannata, Dara
Sun, Hui
Beth On, Mordechay
Liu, Chengyu
Jasper, Hector Guillermo
Domené, Horacio
Karabatas, Liliana Margarita
Guida, Clara
Basta Pljakic, Jelena
Cardoso, Luis
Rosen, Clifford J.
Frystyk, Jan
Yakar, Shoshana
author_role author
author2 Wu, Yingjie
Courtland, Hayden William
Cannata, Dara
Sun, Hui
Beth On, Mordechay
Liu, Chengyu
Jasper, Hector Guillermo
Domené, Horacio
Karabatas, Liliana Margarita
Guida, Clara
Basta Pljakic, Jelena
Cardoso, Luis
Rosen, Clifford J.
Frystyk, Jan
Yakar, Shoshana
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv insulin-like growth factor-1 (IGF1)
IGF1 bioactivity
knock-in mouse models of mutated IGF1
topic insulin-like growth factor-1 (IGF1)
IGF1 bioactivity
knock-in mouse models of mutated IGF1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Understanding insulin-like growth factor-1 (IGF1) biology is of particular importance because, apart from its role in mediating growth, it plays key roles in cellular transformation, organ regeneration, immune function, development of the musculoskeletal system and aging. IGF1 bioactivity is modulated by its binding to IGF-binding proteins (IGFBPs) and the acid labile subunit (ALS), which are present in serum and tissues. To determine whether IGF1 binding to IGFBPs is necessary to facilitate normal growth and development, we used a gene-targeting approach and generated two novel knock-in mouse models of mutated IGF1, in which the native Igf1 gene was replaced by Des-Igf1 (KID mice) or R3-Igf1 (KIR mice). The KID and KIR mutant proteins have reduced affinity for the IGFBPs, and therefore present as unbound IGF1, or ‘free IGF1’. We found that both KID and KIR mice have reduced serum IGF1 levels and a concomitant increase in serum growth hormone levels. Ternary complex formation of IGF1 with the IGFBPs and the ALS was markedly reduced in sera from KID and KIR mice compared with wild type. Both mutant mice showed increased body weight, body and bone lengths, and relative lean mass. We found selective organomegaly of the spleen, kidneys and uterus, enhanced mammary gland complexity, and increased skeletal acquisition. The KID and KIR models show unequivocally that IGF1-complex formation with the IGFBPs is fundamental for establishing normal body and organ size, and that uncontrolled IGF bioactivity could lead to pathological conditions.
Fil: Elis, Sebastien. Mount Sinai School of Medicine; Estados Unidos
Fil: Wu, Yingjie. Mount Sinai School of Medicine; Estados Unidos
Fil: Courtland, Hayden William. Mount Sinai School of Medicine; Estados Unidos
Fil: Cannata, Dara. Mount Sinai School of Medicine; Estados Unidos
Fil: Sun, Hui. Mount Sinai School of Medicine; Estados Unidos
Fil: Beth On, Mordechay. Mount Sinai School of Medicine; Estados Unidos
Fil: Liu, Chengyu. National Institutes of Health; Estados Unidos
Fil: Jasper, Hector Guillermo. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Domené, Horacio. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina
Fil: Karabatas, Liliana Margarita. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Guida, Clara. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina
Fil: Basta Pljakic, Jelena. City University Of New York. The City College Of New York.; Estados Unidos
Fil: Cardoso, Luis. City University Of New York. The City College Of New York.; Estados Unidos
Fil: Rosen, Clifford J.. Maine Medical Center Research Institute; Estados Unidos
Fil: Frystyk, Jan. Aarhus University Hospital; Dinamarca
Fil: Yakar, Shoshana. Mount Sinai School of Medicine; Estados Unidos
description Understanding insulin-like growth factor-1 (IGF1) biology is of particular importance because, apart from its role in mediating growth, it plays key roles in cellular transformation, organ regeneration, immune function, development of the musculoskeletal system and aging. IGF1 bioactivity is modulated by its binding to IGF-binding proteins (IGFBPs) and the acid labile subunit (ALS), which are present in serum and tissues. To determine whether IGF1 binding to IGFBPs is necessary to facilitate normal growth and development, we used a gene-targeting approach and generated two novel knock-in mouse models of mutated IGF1, in which the native Igf1 gene was replaced by Des-Igf1 (KID mice) or R3-Igf1 (KIR mice). The KID and KIR mutant proteins have reduced affinity for the IGFBPs, and therefore present as unbound IGF1, or ‘free IGF1’. We found that both KID and KIR mice have reduced serum IGF1 levels and a concomitant increase in serum growth hormone levels. Ternary complex formation of IGF1 with the IGFBPs and the ALS was markedly reduced in sera from KID and KIR mice compared with wild type. Both mutant mice showed increased body weight, body and bone lengths, and relative lean mass. We found selective organomegaly of the spleen, kidneys and uterus, enhanced mammary gland complexity, and increased skeletal acquisition. The KID and KIR models show unequivocally that IGF1-complex formation with the IGFBPs is fundamental for establishing normal body and organ size, and that uncontrolled IGF bioactivity could lead to pathological conditions.
publishDate 2011
dc.date.none.fl_str_mv 2011-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/103584
Elis, Sebastien; Wu, Yingjie; Courtland, Hayden William; Cannata, Dara; Sun, Hui; et al.; Unbound (bioavailable) IGF1 enhances somatic growth; Company of Biologists; Disease Models And Mechanisms; 4; 4-2011; 649-658
1754-8403
1754-8411
CONICET Digital
CONICET
url http://hdl.handle.net/11336/103584
identifier_str_mv Elis, Sebastien; Wu, Yingjie; Courtland, Hayden William; Cannata, Dara; Sun, Hui; et al.; Unbound (bioavailable) IGF1 enhances somatic growth; Company of Biologists; Disease Models And Mechanisms; 4; 4-2011; 649-658
1754-8403
1754-8411
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://dmm.biologists.org/cgi/pmidlookup?view=long&pmid=21628395
info:eu-repo/semantics/altIdentifier/doi/10.1242/dmm.006775
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Company of Biologists
publisher.none.fl_str_mv Company of Biologists
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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