Unbound (bioavailable) IGF1 enhances somatic growth
| Autor: | Luis Cardoso, Hui Sun, Jan Frystyk, Hayden William Courtland, Liliana Karabatas, Chengyu Liu, Sebastien Elis, Jelena Basta-Pljakic, Shoshana Yakar, Mordechay Beth-On, Hector Jasper, Yingjie Wu, Clifford J. Rosen, Horacio Domene, Dara Cannata, Clara Guida |
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| Přispěvatelé: | Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai [New York] (MSSM), National Institutes of Health, Ricardo Gutierrez Children's Hospital, Partenaires INRAE, City College of New York, Maine Medical Center Research Institute (MMCRI), Aarhus University [Aarhus], NIH, United States AR054919 AR055141, NIH/NIA, United States AG034198, NIH/HLI, United States HL101157, NSF/MRI, United States CBET-0723027, NIH/NIAMS, United States AR53853 AR45433, Argentina CONICET PIP 11420090100045 |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Somatic cell
Mutant Uterus Medicine (miscellaneous) Ciencias de la Salud lcsh:Medicine Plasma protein binding souris Mice 0302 clinical medicine Immunology and Microbiology (miscellaneous) IGF1 bioactivity Osteogenesis développement corporel knock-in mouse models of mutated IGF1 Body Size Gene Knock-In Techniques Insulin-Like Growth Factor I Peptide sequence Ternary complex 0303 health sciences Organ Size 3. Good health Otras Ciencias de la Salud medicine.anatomical_structure 030220 oncology & carcinogenesis Models Animal purl.org/becyt/ford/3 [https] Female Growth and Development hormones hormone substitutes and hormone antagonists lcsh:RB1-214 Autre (Sciences du Vivant) Research Article Protein Binding medicine.medical_specialty [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT] endocrine system CIENCIAS MÉDICAS Y DE LA SALUD education Molecular Sequence Data Neuroscience (miscellaneous) Biological Availability 030209 endocrinology & metabolism Spleen Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences purl.org/becyt/ford/3.3 [https] Immune system Mammary Glands Animal Internal medicine medicine lcsh:Pathology Animals Amino Acid Sequence Gene 030304 developmental biology Base Sequence lcsh:R Body Weight Wild type Cell Biology facteur de croissance igf 1 Mice Mutant Strains Mice Inbred C57BL Endocrinology insulin-like growth factor-1 (IGF1) Growth Hormone Multiprotein Complexes |
| Zdroj: | Elis, S, Wu, Y, Courtland, H-W, Cannata, D, Sun, H, Beth-On, M, Liu, C, Jasper, H, Domené, H, Karabatas, L, Guida, C, Basta-Pljakic, J, Cardoso, L, Rosen, C J, Frystyk, J & Yakar, S 2011, ' Unbound (bioavailable) IGF1 enhances somatic growth ', Disease Models and Mechanisms, vol. 4, no. 5, pp. 649-58 . https://doi.org/10.1242/dmm.006775 Disease Models & Mechanisms Disease Models & Mechanisms, Cambridge Company of Biologists, 2011, 4 (5), pp.649-658. ⟨10.1242/dmm.006775⟩ CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Disease Models and Mechanisms 5 (4), 649-658. (2011) Disease Models & Mechanisms, Vol 4, Iss 5, Pp 649-658 (2011) |
| ISSN: | 1754-8403 1754-8411 |
| DOI: | 10.1242/dmm.006775 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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