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dc.contributor.author
Elis, Sebastien  
dc.contributor.author
Wu, Yingjie  
dc.contributor.author
Courtland, Hayden William  
dc.contributor.author
Cannata, Dara  
dc.contributor.author
Sun, Hui  
dc.contributor.author
Beth On, Mordechay  
dc.contributor.author
Liu, Chengyu  
dc.contributor.author
Jasper, Hector Guillermo  
dc.contributor.author
Domené, Horacio  
dc.contributor.author
Karabatas, Liliana Margarita  
dc.contributor.author
Guida, Clara  
dc.contributor.author
Basta Pljakic, Jelena  
dc.contributor.author
Cardoso, Luis  
dc.contributor.author
Rosen, Clifford J.  
dc.contributor.author
Frystyk, Jan  
dc.contributor.author
Yakar, Shoshana  
dc.date.available
2020-04-24T19:42:39Z  
dc.date.issued
2011-04  
dc.identifier.citation
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  
dc.identifier.issn
1754-8403  
dc.identifier.uri
http://hdl.handle.net/11336/103584  
dc.description.abstract
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.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Company of Biologists  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
insulin-like growth factor-1 (IGF1)  
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IGF1 bioactivity  
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knock-in mouse models of mutated IGF1  
dc.subject.classification
Otras Ciencias de la Salud  
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Ciencias de la Salud  
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CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
Unbound (bioavailable) IGF1 enhances somatic growth  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2020-02-07T13:40:51Z  
dc.identifier.eissn
1754-8411  
dc.journal.volume
4  
dc.journal.pagination
649-658  
dc.journal.pais
Reino Unido  
dc.journal.ciudad
Cambridge  
dc.description.fil
Fil: Elis, Sebastien. Mount Sinai School of Medicine; Estados Unidos  
dc.description.fil
Fil: Wu, Yingjie. Mount Sinai School of Medicine; Estados Unidos  
dc.description.fil
Fil: Courtland, Hayden William. Mount Sinai School of Medicine; Estados Unidos  
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Fil: Cannata, Dara. Mount Sinai School of Medicine; Estados Unidos  
dc.description.fil
Fil: Sun, Hui. Mount Sinai School of Medicine; Estados Unidos  
dc.description.fil
Fil: Beth On, Mordechay. Mount Sinai School of Medicine; Estados Unidos  
dc.description.fil
Fil: Liu, Chengyu. National Institutes of Health; Estados Unidos  
dc.description.fil
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  
dc.description.fil
Fil: Domené, Horacio. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina  
dc.description.fil
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  
dc.description.fil
Fil: Guida, Clara. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina  
dc.description.fil
Fil: Basta Pljakic, Jelena. City University Of New York. The City College Of New York.; Estados Unidos  
dc.description.fil
Fil: Cardoso, Luis. City University Of New York. The City College Of New York.; Estados Unidos  
dc.description.fil
Fil: Rosen, Clifford J.. Maine Medical Center Research Institute; Estados Unidos  
dc.description.fil
Fil: Frystyk, Jan. Aarhus University Hospital; Dinamarca  
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Fil: Yakar, Shoshana. Mount Sinai School of Medicine; Estados Unidos  
dc.journal.title
Disease Models And Mechanisms  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://dmm.biologists.org/cgi/pmidlookup?view=long&pmid=21628395  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1242/dmm.006775