Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r)

Liu, Jeh-Ping; Baker, Julie C.; Perkins, Archlbald S.; Robertson, Elizabeth J.; Efstratiadis, Argiris

doi:10.1016/s0092-8674(05)80084-4

Cited by 1,682 publications

(1,531 citation statements)

References 49 publications

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“…Igf1r-deficient embryos are significantly smaller in body length and they did not advance beyond a developmental stage equivalent to approximately 18 hpf in wild-type zebrafish but exhibited no patterning defects. These phenotypes are consistent with those reported in mutant mice 11,12,23 and Drosophila 24 but differ from previous studies in Xenopus. 15,16 Although IGF signaling was proposed to be an anteriorizing or neural induction signal in Xenopus, 15,16 our results show that reduction of Igf signaling not only affects retina, but also other tissues throughout the zebrafish embryo.…”

Section: Discussionsupporting

confidence: 90%

“…In agreement with our findings in zebrafish, igf1r null mutant mice exhibit no significant differences in growth rate compared to wild-type littermates until embryonic day 11.0. 11,12 Whether elevated apoptosis played any role in these defects in developmental timing was not investigated. In this study, we found that overexpression of bcl2l could not restore normal developmental timing, suggesting that elevated apoptosis is unlikely the cellular basis underlying the developmental arrest.…”

Section: Discussionmentioning

confidence: 99%

“…They also exhibited global organ hypoplasia and developmental retardation, with no loss of any organ or patterning abnormalities. 11,12 It has thus been concluded that IGF1R signaling is a central regulator of somatic growth in mammals.…”

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confidence: 99%

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Insulin-like growth factor signaling regulates zebrafish embryonic growth and development by promoting cell survival and cell cycle progression

et al. 2007

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Although much is known about the global effects of insulin-like growth factor 1 receptor (IGF1R)-mediated signaling on fetal growth and the clinical manifestations resulting from IGF/IGF1R deficiencies, we have an incomplete understanding of the cellular actions of this essential pathway during vertebrate embryogenesis. In this study, we inhibited IGF1R signaling during zebrafish embryogenesis using antisense morpholino oligonucleotides or a dominant-negative IGF1R fusion protein. IGF1R inhibition resulted in reduced embryonic growth, arrested development and increased lethality. IGF1R-deficient embryos had significant defects in the retina, inner ear, motoneurons and heart. No patterning abnormalities, however, were found in the brain or other embryonic tissues. At the cellular level, IGF1R inhibition increased caspase 3 activity and induced neuronal apoptosis. Coinjection of antiapoptotic bcl2-like mRNA attenuated the elevated apoptosis and rescued the retinal and motoneuron defects, but not the developmental arrest. Subsequent cell cycle analysis indicated an increased percentage of cells in G1 and a decreased percentage in S phase in IGF1R-deficient embryos independent of apoptosis. These results provide novel insight into the cellular basis of IGF1R function and show that IGF1R signaling does not function as an anteriorizing signal but regulates embryonic growth and development by promoting cell survival and cell cycle progression.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Insulin-like growth factor signaling regulates zebrafish embryonic growth and development by promoting cell survival and cell cycle progression

et al. 2007

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“…The addition of IGF‐1 to embryonic IGF‐1 deficient lungs cultured ex vivo increases airway septa remodelling and distal epithelium maturation (S70). Mice with a homozygous null mutation of the IGF‐1 gene have atelectatic lungs and high postnatal mortality due to lung collapse and respiratory failure (28,S75,S76).…”

Section: Organ‐specific Roles Of Igf‐1 In the Foetusmentioning

confidence: 99%

Insulin‐like growth factor 1 has multisystem effects on foetal and preterm infant development

et al. 2016

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Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin‐like growth factor 1 (IGF‐1) axis is the major hormonal mediator of growth in utero, and levels of IGF‐1 are often very low after preterm birth. We reviewed the role of IGF‐1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF‐1 deficiency in preterm morbidities.ConclusionThere is a rationale for clinical trials to evaluate the potential benefits of IGF‐1 replacement in very preterm infants.

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“…Likewise, inactivating mutations of genes leading to deregulated mTORC‐1 activity and failed metabolic checkpoints cause syndromes characterized by multiple, tumor‐like outgrowths in humans, such as Cowden syndrome (Liaw et al, 1997) and tuberous sclerosis (Brook‐Carter et al, 1994). Conversely, experimental knockout of a number of genes involved in PI3K activation and its downstream effectors causes organ hypoplasia and reduced body size in mice (Liu et al, 1993; Dummler et al, 2006). mTORC‐1 is a pivotal sensor of nutrient availability and stress conditions (Ellisen, 2005; Gwinn et al, 2008; Saqcena et al, 2013).…”

mentioning

confidence: 99%

Amyloid Precursor Protein (APP) Affects Global Protein Synthesis in Dividing Human Cells

Sobol¹,

Galluzzo²,

Liang³

et al. 2015

Journal Cellular Physiology

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Hypoxic non‐small cell lung cancer (NSCLC) is dependent on Notch‐1 signaling for survival. Targeting Notch‐1 by means of γ‐secretase inhibitors (GSI) proved effective in killing hypoxic NSCLC. Post‐mortem analysis of GSI‐treated, NSCLC‐burdened mice suggested enhanced phosphorylation of 4E‐BP1 at threonines 37/46 in hypoxic tumor tissues. In vitro dissection of this phenomenon revealed that Amyloid Precursor Protein (APP) inhibition was responsible for a non‐canonical 4E‐BP1 phosphorylation pattern rearrangement—a process, in part, mediated by APP regulation of the pseudophosphatase Styx. Upon APP depletion we observed modifications of eIF‐4F composition indicating increased recruitment of eIF‐4A to the mRNA cap. This phenomenon was supported by the observation that cells with depleted APP were partially resistant to silvestrol, an antibiotic that interferes with eIF‐4A assembly into eIF‐4F complexes. APP downregulation in dividing human cells increased the rate of global protein synthesis, both cap‐ and IRES‐dependent. Such an increase seemed independent of mTOR inhibition. After administration of Torin‐1, APP downregulation and Mechanistic Target of Rapamycin Complex 1 (mTORC‐1) inhibition affected 4E‐BP1 phosphorylation and global protein synthesis in opposite fashions. Additional investigations indicated that APP operates independently of mTORC‐1. Key phenomena described in this study were reversed by overexpression of the APP C‐terminal domain. The presented data suggest that APP may be a novel regulator of protein synthesis in dividing human cells, both cancerous and primary. Furthermore, APP appears to affect translation initiation using mechanisms seemingly dissimilar to mTORC‐1 regulation of cap‐dependent protein synthesis. J. Cell. Physiol. 230: 1064–1074, 2015. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

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Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r)

Cited by 1,682 publications

References 49 publications

Insulin-like growth factor signaling regulates zebrafish embryonic growth and development by promoting cell survival and cell cycle progression

Insulin-like growth factor signaling regulates zebrafish embryonic growth and development by promoting cell survival and cell cycle progression

Insulin‐like growth factor 1 has multisystem effects on foetal and preterm infant development

Amyloid Precursor Protein (APP) Affects Global Protein Synthesis in Dividing Human Cells

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